Physical Activity and Health
Edited by Claude Bouchard, Steven N. Blair and William L. Haskell
456 Pages
The human body is designed for activity. For most of our history, physical activity was required for survival, but technological advances have eliminated much of the need for hard physical labor. As our activity levels have dropped, it has become clear that a physically inactive lifestyle can lead to a host of health problems. Physical Activity and Health, Second Edition, provides a comprehensive treatment of the research on the benefits of a physically active lifestyle in comparison with the harmful consequences of physical inactivity.
Written by leading scientists from the United States, Canada, Europe, and Australia, Physical Activity and Health, Second Edition, brings together the results of the most important studies on the relationship between physical activity, sedentarism, and various health outcomes. The second edition has been fully updated based on the latest advances in this rapidly changing field and expanded to include the following new content:
• A chapter on the physiology of inactivity and the effects of sedentary behavior even in people who engage in appropriate amounts of physical activity, which is an area of growing interest
• More extensive coverage of physical activity, aging, and the brain, including a new chapter on the relationship between physical activity and brain structures and functions
• A chapter on the development of national and international physical activity and health guidelines, which will help readers better understand how scientific findings are converted into practical recommendations
Physical Activity and Health, Second Edition, offers a detailed yet concise presentation of key concepts as well as a framework to help readers relate results from single studies or collections of studies to the overall paradigm linking physical activity and physical fitness to health. For each of the topics covered, the text provides an overview of the most important research findings, discusses the limitations of the current knowledge base, and identifies directions for future investigation.
At the core of the text is a review of our current understanding of how physical activity affects health concerns such as cardiovascular disease, diabetes, cancer, and obesity as well as aging and mental health. The text identifies sedentary living habits and poor fitness as major public health problems and examines the potential of physical activity to prevent disease and enhance quality of life. This complete resource also looks at the evolution of the field of physical activity and health; variations in physical activity levels across age, sex, and ethnic groups; the body’s physiological responses to physical activity; dose-response issues; and the influence of genetics on physical activity, fitness, and health. The book ends with an integration of the issues covered and discusses new opportunities for research.
The second edition of Physical Activity and Health continues to offer clear, user-friendly coverage of the most important concepts and research in the field. Numerous special features will aid readers in their comprehension of the material. Chapter outlines and callout boxes help readers key in on important topics and focus their reading, and chapter summaries, definitions of key terms, and study questions provide tools for review and self-testing. Commonly used acronyms and abbreviations are found on the interior covers for handy reference.
Where other books have simply promoted physical activity for the individual or a population, Physical Activity and Health, Second Edition, completely integrates current knowledge of the relationship between physical activity and health. With contributions from some of the finest scientists in the field, this comprehensive text offers information unmatched in accuracy and reliability.
Part I: History and Current Status of the Study of Physical Activity and Health
Chapter 1: Why Study Physical Activity and Health?
Claude Bouchard, PhD; Steven N. Blair, PED; and William L. Haskell, PhD
Human Evolution, History, and Physical Activity
Burden of Chronic Diseases
Health and Its Determinants
Aging and Health
Defining Physical Activity and Physical Fitness
Physical Inactivity Versus Physical Activity
Summary
Review Materials
Chapter 2: Historical Perspectives on Physical Activity, Fitness, and Health
Russell R. Pate, PhD
Early Beliefs About Physical Activity and Health
Scientific Inquiry on Exercise and Health
Evolution of Physical Activity Guidelines
Summary
Review Materials
Chapter 3: Physical Activity and Fitness With Age, Sex, and Ethnic Differences
Peter T. Katzmarzyk, PhD, FACSM
Physical Activity
Physical Fitness
Summary
Review Materials
Chapter 4: Sedentary Behavior and Inactivity Physiology
Marc Hamilton, PhD; and Neville Owen, PhD
Sedentary Behavior, Physical Activity, and Public Health
Inactivity Physiology: The Underlying Biology of Acute and Chronic Muscular Inactivity
Sedentary Behavior and Metabolic Health: Emerging Epidemiological Evidence
Humans May Not Have Reached the Pinnacle of Physical Inactivity
A Comprehensive Sedentary Behavior Research Agenda
Public Health Implications
Summary
Review Materials
Part II: Effects of Physical Activity on the Human Organism
Chapter 5: Metabolic, Cardiovascular, and Respiratory Responses to Physical Activity
Edward T. Howley, PhD
Relationship of Energy to Physical Activity
Oxygen Consumption and Cardiovascular and Respiratory Responses to Exercise
Effect of Training, Age, and Gender on Maximal Oxygen Uptake
Application to Exercise Training and Physical Activity Interventions
Summary
Review Materials
Chapter 6: Acute Responses to Physical Activity and Exercise
Adrianne E. Hardman, MSc, PhD
Lipids and Lipoproteins
Endothelial Function
Insulin–Glucose Dynamics
Blood Pressure
Hematological Changes
Immune Function and Inflammation
Responses Related to Energy Balance
Augmentation of Acute Effects by Training
Summary
Review Materials
Chapter 7: Hormonal Response to Regular Physical Activity
Peter A. Farrell, PhD
Defining Hormones
Importance of Hormonal Regulation
Regular Physical Activity and Hormonal Adaptations
Summary
Review Materials
Chapter 8: Skeletal Muscle Adaptation to Regular Physical Activity
Howard J. Green, PhD
Skeletal Muscle and Human Survival
Muscle Cell: Composition, Structure, and Function
Muscle Fiber Types and Subtypes
Muscle Adaptation and Functional Consequences
Aging Muscle: The Role of Training
Summary
Review Materials
Chapter 9: Response of Liver, Kidney, and Other Organs and Tissues to Regular Physical Activity
Roy J. Shephard, MB, BS, MD (London), PhD, DPE
Acute Effects of Physical Activity
Chronic Effects of Physical Activity
Strengths and Limitations of the Current Evidence
Summary
Review Materials
Part III: Physical Activity, Fitness, and Health
Chapter 10: Physical Activity, Fitness, and Mortality Rates
Michael J. LaMonte, PhD; and Steven N. Blair, PED
Physical Activity and Mortality
Fitness and Mortality
Activity or Fitness and Mortality in Adults With Existing Diseases
Quantifying the Population Mortality Burden of Inactivity
Summary
Review Materials
Chapter 11: Physical Activity, Fitness, and Cardiac, Vascular, and Pulmonary Morbidities
Ian Janssen, PhD
Low Physical Activity and Low Cardiorespiratory Fitness as Risk Factors for Cardiovascular Morbidities
Low Physical Activity and Low Cardiorespiratory Fitness as Risk Factors for Pulmonary Morbidities
Biological Mechanisms
Role of Physical Activity in Patients with Cardiac, Vascular, and Pulmonary Morbidities
Summary
Review Materials
Chapter 12: Physical Activity, Fitness, and Obesity
Robert Ross, PhD; and Ian Janssen, PhD
Definition and Problem of Overweight and Obesity
Fat Depots
Relationships Among Excess Weight, Physical Activity, and Fitness
Role of Physical Activity in Prevention and Treatment of Excess Weight
Summary
Review Materials
Chapter 13: Physical Activity, Fitness, and Diabetes Mellitus
R. Jan-Willem Middelbeek, MD, MS; Oscar Alcazar, PhD; and Laurie J. Goodyear, PhD
Diabetes: Definitions and Prevalence
Epidemiology, Etiology, and Complications of Type 2 Diabetes
Impact of Physical Activity on Insulin and Glucose Metabolism
Epidemiological Evidence Indicating Benefits of Physical Activity in Preventing Type 2 Diabetes
Summary of Randomized Controlled Trials on the Prevention of Type 2 Diabetes
Importance of Regular Physical Activity for People With Type 2 Diabetes
Summary
Review Materials
Chapter 14: Physical Activity, Fitness, and Cancer
I-Min Lee, MBBS, ScD
Importance of Cancer
How Physical Activity and Physical Fitness Decrease the Risk of Developing Cancer
How We Study Whether Physical Activity and Physical Fitness Decrease the Risk of Developing Cancer
Physical Activity, Physical Fitness, and Site-Specific Cancers
Physical Activity and Cancer Survivors
Summary
Review Materials
Chapter 15: Physical Activity, Fitness, and Joint and Bone Health
Jennifer Hootman, PhD, ATC, FACSM, FNATA
Scientific Evidence
Strengths and Limitations of the Evidence
Summary
Review Materials
Chapter 16: Physical Activity, Muscular Fitness, and Health
Neil McCartney, PhD; and Stuart Phillips, PhD
History of Resistance Training and Its Role in Health
Fundamental Aspects of Resistance Training
Resistance Training Throughout the Life Span
Resistance Training in Disease and Disability
Summary
Review Materials
Chapter 17: Physical Activity, Fitness, and Children
Thomas Rowland, MD
Understanding the Exercise–Health Link in Children
Defining the Kinds and Amount of Physical Activities for Health
Optimal Intervention Strategies
Biological Effects on Physical Activity in Youth
Summary
Review Materials
Chapter 18: Risks of Physical Activity
Evert A.L.M. Verhagen, PhD; Esther M.F. van Sluijs, PhD; and Willem van Mechelen, MD, PhD
Risks of Physical Activity and Sport Participation
Minimizing Risk and Maximizing Benefits
Recommendations for Future Research
Summary
Review Materials
Part IV: Physical Activity, Fitness, Aging, and Brain Functions
Chapter 19: Physical Activity, Fitness, and Aging
Loretta DiPietro, PhD, MPH
The Aging Process
Methodological Considerations in Aging Research
Demographics of Physical Activity Among Older Adults
Dimensions of Physical Activity and Their Relationship to Health and Function in Aging
Programmatic Issues in Promoting Physical Activity in Older Populations
Summary
Review Materials
Chapter 20: Physical Activity and Brain Functions
Kirk I. Erickson, PhD
Descriptive Questions
Mechanistic Questions
Applied Questions: Populations Benefiting From Physical Activity
Moderating Questions: Factors Moderating the Effect of Physical Activity
Summary
Review Materials
Chapter 21: Exercise and Its Effects on Mental Health
John S. Raglin, PhD; and Gregory S. Wilson, PED, FACSM
Research Paradigms of Exercise and Mental Health Research
Exercise and Depression
Exercise and Anxiety
Exercise and Schizophrenia
Putative Mechanisms for the Psychological Benefits of Exercise
Detrimental Psychological Responses to Exercise: The Overtraining Syndrome
Summary
Review Materials
Part V: How Much Is Required and How Do We Get There?
Chapter 22: Dose–Response Issues in Physical Activity, Fitness, and Health
William L. Haskell, PhD
Principles Guiding the Body’s Response to Activity
Components of the Physical Activity Dose
Factors Determining Optimal Activity Dose
Physical Activity and Fitness: Dose for Health Benefits
Summary
Review Materials
Chapter 23: From Science to Physical Activity Guidelines
Mark S. Tremblay, PhD; and William L. Haskell, PhD
Stages of Physical Activity Guideline Development
Strengths, Limitations, and Challenges
Summary
Review Materials
Part VI: New Challenges and Opportunities
Chapter 24: Genetic Differences in the Relationships Among Physical Activity, Fitness, and Health
Tuomo Rankinen, PhD; and Claude Bouchard, PhD
Basics of Human Genetics
Events in Human Genes and Genomes
Genetic Variation in Exercise Traits Among Sedentary People
Genetics of Physical Activity Level
Individual Differences in Response to Regular Exercise
Genes and Responses to Exercise
Trait-Specific Response to Exercise
Personalized Exercise Medicine
Summary
Review Materials
Chapter 25: An Integrated View of Physical Activity, Fitness, and Health
William L. Haskell, PhD; Steven N. Blair, PED; and Claude Bouchard, PhD
Physical Activity Versus Inactivity: Universal Value Versus Damaging Consequences
Developing and Implementing Physical Activity Plans
Research Questions and Issues
Summary
Review Materials
Claude Bouchard, PhD, is the director of the Human Genomics Laboratory at Pennington Biomedical Research Center, a campus of the Louisiana State University System, where he also holds the John W. Barton Sr. chair in genetics and nutrition. He was director of the Physical Activity Sciences Laboratory at Laval University, Quebec City, Canada, for over 20 years. Dr. Bouchard holds a BPed from Laval University, an MSc in exercise physiology from the University of Oregon at Eugene, and a PhD in population genetics from the University of Texas at Austin.
For four decades, his research has dealt with the role of physical activity, and the lack thereof, on physiology, metabolism, and indicators of health, taking into account genetic uniqueness. He has performed research on the contributions of gene sequence variation and the benefits to be expected from regular activity in terms of changes in cardiovascular and diabetes risk factors
Dr. Bouchard has served as program leader for four consensus conferences and symposia pertaining to various aspects of physical activity and health. He has published more than 1,000 scientific papers and has edited several books and monographs dealing with physical activity and health.
Dr. Bouchard is the recipient of the Willendorf Award from the International Association for the Study of Obesity, the Sandoz Award from the Canadian Atherosclerosis Society, the Albert Creff Award of the National Academy of Medicine of France, and four honoris causa doctorates (Katholieke Universiteit Leuven, University of South Carolina, University of Guelph, and Brock University). He is a foreign member of the Royal Academy of Medicine of Belgium and a member of the Order of Canada.
Dr. Bouchard is former president of the Canadian Society for Applied Physiology, the North American Association for the Study of Obesity, and the International Association for the Study of Obesity. He is a fellow of the American College of Sports Medicine, the American Heart Association, the American Society of Nutrition, and the American Association for the Advancement of Science.
Steven N. Blair, PED, was a distinguished professor emeritus in the departments of exercise science and epidemiology and biostatistics at the Arnold School of Public Health at the University of South Carolina. His research focused on the associations between lifestyle and health, with a specific emphasis on exercise, physical fitness, body composition, and chronic disease. Listed as one of the world’s most influential scientific minds by Thomson Reuters, Blair published more than 700 papers and chapters in scientific literature. With over 60,000 citations of his body of work (h-index of 114), he was one of the most highly cited exercise scientists.
Blair was a fellow of the American College of Epidemiology, Society of Behavioral Medicine, American College of Sports Medicine, American Heart Association, Obesity Society, and European Society of Preventive Medicine. He was a retired fellow of the Royal Society of Medicine–London and the National Academy of Kinesiology A past president of the American College of Sports Medicine, National Coalition for Promoting Physical Activity, and the National Academy of Kinesiology, he received four honorary doctoral degrees. He received awards from many professional associations, including a MERIT Award from the National Institutes of Health, an Honor Award from the American College of Sports Medicine, and a Population Science Award from the American Heart Association. He was one of the few individuals outside the U.S. Public Health Service to be awarded the Surgeon General's Medallion.
Steven Blair passed away in 2023.
William L. Haskell, PhD, is emeritus professor of medicine in the Stanford Prevention Research Center and the Division of Cardiovascular Medicine, Stanford School of Medicine. He holds an honorary MD degree from Linkoping University in Sweden.
For more than 40 years, his research has investigated the relationships between physical activity and health. He has been involved at the national and international levels in the development of physical activity and fitness guidelines and recommendations for physical activity in health promotion and disease prevention.
Dr. Haskell has served as principal investigator on major NIH-funded research projects demonstrating the health benefits of physical activity. For the past 17 years, he has been a member of the planning committee and faculty for the CDC-sponsored research course on physical activity and public health. From 1968 to 1970, he was program director for the President's Council on Physical Fitness and Sports. He also served as chair of the Physical Activity Guidelines Advisory Committee for the U.S. Department of Health and Human Services, which documented the scientific basis for the 2008 Physical Activity Guidelines for Americans. From 2008 to 2010 he was a scientific advisor to the World Health Organization for the development of Global Recommendations on Physical Activity for Health (2010) and to the United Kingdom Health Ministries for the development of physical activity and sedentary behavior guidelines for the home countries. Currently he is chair of the International Review Panel for the Evaluation of Exercise and Sports Sciences in the Nordic Countries.
He is past president of the American College of Sports Medicine and founder and past president of the American College of Sports Medicine Foundation. He was a fellow with the Exercise and Rehabilitation Council, American Heart Association, and American Association of Cardiovascular and Pulmonary Rehabilitation.
“With the vast number of topics it covers as well as the examples of the practical application of the underlying principles it presents, this book is an excellent learning and teaching resource.”
-- Doody’s Book Review (5 star review)
What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar 
findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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What role does genetics play in physical activity
While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals’ propensity to be physically active or sedentary.
Genetics of Physical Activity Level
Regular physical activity is a central component of current public health recommendations. While psychological, social, and environmental factors contribute significantly to physical activity behavior, it is important to recognize that activity behavior also has a biological basis and that genetic variation could affect individuals' propensity to be physically active or sedentary. Twin studies, as well as studies in nuclear and extended families, have provided maximal heritability estimates ranging from 15% to 60% for total physical activity level as well as for sedentarism, leisure-time activity, and sport participation.
At this point it would be helpful to introduce genome-wide association studies (GWAS). Rapid technical improvements in microarray-based high-throughput genotyping methods have made it possible to assay hundreds of thousands of SNPs in a single reaction, allowing detailed GWAS. A typical GWAS relies on a large number of SNPs that are distributed evenly across the genome, using either a case-control or a cohort study design. Associations between the trait of interest and each SNP are tested using standard statistical methods. However, because of the large number of tests in a GWAS, criteria for statistical significance have to be modified. For example, in a GWAS with 1 million SNPs, the threshold of genome-wide statistical significance is p < 5 × 10−8.
Data on the molecular genetics of physical activity levels in humans are still scarce, although the first GWAS for activity level was published in 2009 (De Moor et al. 2009). The report included results from two cohort studies: 1,644 unrelated individuals from the Netherlands Twin Register and 978 subjects living in Omaha, Nebraska. None of the 1.6 million SNPs reached the commonly used threshold of genome-wide significance (p = 5 × 10−8), although SNPs in three genomic regions showed p-values less than 1 × 10−5. The strongest associations were observed on chromosome 10q23.2 at the 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) gene locus: The odds ratio (OR) for being an exerciser was 1.32 (p = 3.81 × 10−6) for the common T-allele of SNP rs10887741. The other two SNPs with p < 1 × 10−5 were rs12612420 (p = 7.61 × 10−6, OR = 1.43), located about 12 kilobases (kb) upstream of the first exon of the DNA polymerase-transactivated protein 6 (DNAPTP6) gene, and rs8097348 (p = 6.68 × 10−6, OR = 1.36), which is located about 236 kb upstream of chromosome 18 open reading frame 2 (C18orf2). The associations with previously reported physical activity candidate genes were explored as well. The strongest candidate gene association was detected with SNP rs12405556 (p = 9.7 × 10−4, OR = 1.24) at the leptin receptor (LEPR) gene locus.
The major advantage of the GWAS strategy is that it is not restricted by a priori hypotheses, as is the case in candidate gene studies. Moreover, with millions of measured and imputed SNPs, a GWAS covers the entire genome uniformly and has sufficient sensitivity to detect small to moderate gene effects of relatively common sequence variants if the sample size is large. A critical feature of genetic studies is replication: Findings of an individual study should be tested in other large cohorts with a similar phenotype and study design. If the associations are replicated, the case for the contribution of a gene and DNA sequence variant to the trait of interest becomes considerably stronger. Given that several large cohort studies with physical activity questionnaire data available have also recently completed GWAS SNP genotyping, we could have interesting new data with replication panels in the near future.
Individual Differences in Response to Regular Exercise
There are marked interindividual differences in the adaptation to exercise training. For example, in the HERITAGE Family Study, 742 healthy but sedentary participants followed an identical, well-controlled endurance training program for 20 weeks. Despite the identical training program, increases in .VO2max varied from no change to increases of more than 1 L/min (figure 24.9). This high degree of heterogeneity in responsiveness to a fully standardized exercise program in the HERITAGE Family Study was not accounted for by age, gender, or ethnic differences. A similar pattern of variation in training responses was observed for several other phenotypes, such as plasma high-density lipoprotein (HDL) cholesterol levels and submaximal exercise heart rate and blood pressure changes (Bouchard and Rankinen 2001). These data underline the notion that the effects of endurance training on cardiovascular and other relevant traits should be evaluated not only in terms of mean changes, but also in terms of response heterogeneity.
A number of questions come to mind as a result of observations such as those depicted in figure 24.9 and the others discussed previously. Are the high and low responses to regular exercise characterized by significant familial aggregation; that is, are there families with mainly low responders and others in which all family members show significant improvements? Is individual variability a normal biological phenomenon reflecting genetic diversity? Can we identify SNPs, genes, and alleles that predict the ability to respond positively or adversely to regular exercise?
Genes and Responses to Exercise
We now turn our attention to the evidence for a role of specific gene and sequence variants in the range of responses to regular exercise. Blood pressure, lipids and lipoproteins, glucose and insulin, and cardiorespiratory endurance response phenotypes are discussed. For editorial considerations, studies reviewed from this point onward in this chapter are not referenced individually. However, the interested reader can find these references in the latest version of the Human Gene Map for Performance and Health-Related Fitness Phenotypes (Bray et al. 2009).
Another example of response heterogeneity relates to skeletal metabolism indicators and comes from the HERITAGE Family Study. The levels of nine enzymes involved in phosphocreatine metabolism, glycolysis, and oxidative metabolism were measured in muscle biopsies obtained before and after a 20-week endurance training program in 78 individuals from 19 nuclear families (Rico-Sanz et al. 2003). Exercise training induced statistically significant increases in all enzyme levels. Furthermore, all training responses showed significant familial aggregation: The between-family variance was 1.85 to 4.0 times greater than the variance within families.
Although exercise-related traits are mainly polygenic and multifactorial in nature, much can be learned from some monogenic disorders characterized by compromised exercise capacity or exercise intolerance. These disorders affect only a few individuals, but they provide interesting examples of genetic defects that have profound effects on the ability to perform physical activity, usually attributable to compromised energy metabolism. Although these genetic defects compromise exercise capacity, there is no evidence that overexpression of these genes leads to improved physical performance. However, it is important to understand the molecular mechanisms contributing to both ends of the distribution of cardiorespiratory endurance and its trainability. Table 24.3 lists some of the genes that have been associated with a decreased exercise capacity (Rankinen et al. 2004).
Genes and Blood Pressure Response to Regular Exercise
The 2007 update of the Human Gene Map for Performance and Health-Related Fitness Phenotypes included 17 genes from 23 studies that have been investigated in relation to exercise training-induced changes in hemodynamic phenotypes (Bray et al. 2009). Findings for 13 candidate genes (AGTR1, AMPD1, APOE, BDKRB2, CHRM2, EDN1, FABP2, GNB3, HBB, KCNQ1, NFKB1, PPARA, TTN) were based on a single study. However, with four candidate genes, the positive associations were reported in at least two studies. For example, in both the HERITAGE Family Study and the DNASCO Study cohorts, the angiotensinogen (AGT) Met235Thr polymorphism (in which threonine is substituted for methionine) was associated with endurance training-induced changes in diastolic blood pressure in men.
Similarly, an association between the angiotensin I converting enzyme (ACE) gene I/D (insertion or deletion of a sequence) polymorphism and training-induced left ventricular (LV) growth has been reported in two studies (figure 24.10) (Montgomery et al. 1997; Myerson et al. 2001). In 1997, Montgomery and coworkers reported that the ACE D-allele was associated with greater increases in LV mass and with septal and posterior wall thickness after 10 weeks of physical training in British Army recruits (figure 24.10a). A similar training paradigm was repeated a few years later, and the training-induced increase in LV mass was 2.7 times greater in the D/D genotype compared with the I/I homozygotes (figure 24.10b).
A third candidate gene with positive evidence of associations from multiple studies is endothelial nitric oxide synthase 3 (NOS3). In the HERITAGE Family Study, homozygotes for the glutamine allele at codon 298 (Glu298) had a reduction in submaximal exercise diastolic blood pressure that was more than three times greater than that of the homozygotes for the asparagine allele (Asp298Asp) after the training program. A similar pattern was evident with the systolic blood pressure and rate-pressure product training responses (Rankinen et al. 2000). In coronary artery disease patients, exercise training significantly improved acetylcholine-induced change in average peak velocity of coronary arteries. However, the training response was significantly blunted in the carriers of the NOS3 -786C allele of a polymorphism located in the 5'-UTR of the NOS3 gene compared with the patients who were homozygotes for the -786T-allele (Erbs et al. 2003).
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Evolution of physical activity guidelines reflects changing body of evidence
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public.
Evolution of Physical Activity Guidelines
Scientific knowledge about physical activity and health is of little value if people cannot understand it and apply it to their lives. For the past three decades, there has been a gradual but steady development in the effort to present information on physical activity and health to the general public. This has come through public health messages known as physical activity guidelines.
Groundwork
Health scientists and practitioners have long believed that regular physical activity is essential to maintain good health. So it is not surprising that for a very long time, individual health professionals and health organizations have been making recommendations regarding the types and amounts of physical activity needed for health and fitness. As emphasized in the preceding section, scientific support for the impact of physical activity on health has developed rapidly in recent decades. As the relevant knowledge base has grown, physical activity recommendations for the public have been modified to maintain consistency with the existing research evidence. In this section, we track the evolution of physical activity guidelines as they have been presented to the public since the 1950s.
In 1957, Finnish researcher Marti Karvonen and his colleagues published the findings of a study that has become a classic in exercise science. Karvonen observed the effects of exercise training via treadmill running on endurance fitness in a small number of male medical students. He reported that training intensity corresponding to a heart rate of at least 60% of the heart rate range (maximum heart rate minus resting heart rate) was required to produce significant gains in cardiorespiratory fitness. Although Karvonen's study was very small and quite limited in its research design, his findings became the platform for exercise guidelines for the ensuing three decades. Karvonen's program was presented in terms of minimums for frequency, duration, and intensity of training. A half century later, it seems remarkable that such a small and limited study could have had such a powerful influence on health practice.
“Heart rate during training has to be more than 60% of the available range from rest to the maximum attainable by running . . . in order to produce a change in the WR [working heart rate]. . . . A decrease of the WR is understood to indicate an increase of the maximum oxygen uptake.”
Karvonen, Kentala, and Mustala 1957, p. 314
Initial Attempts to Speak to the Public
During the 1960s, two American men, one a track coach and the other a physician, published books that brought practical physical activity guidelines to the masses. In 1963, Bill Bowerman, coach of the University of Oregon's track team, visited a coaching colleague in New Zealand, where he witnessed many middle-aged adults running for health and fitness. He was so impressed by what he had seen that on his return to the United States, he wrote Jogging, a small paperback volume that has often been credited with launching a fitness revolution (Bowerman and Harris 1967). Bowerman described a slow running program that emphasized gradual, progressive increases in distance and frequency of exercise. His basic recommendation was that almost everyone can benefit from “an exercise program of relaxed walking and running” and that jogging is something that almost everyone can do.
In 1968, only a year after Bowerman popularized jogging as a specific form of exercise, Dr. Kenneth Cooper, then an Air Force physician, published Aerobics, a book in which he laid out a simple point system for determining how much exercise should be accumulated on a weekly basis. With his Aerobics Point System he recommended that adults accumulate a minimum of 30 points per week. Cooper recommended that sedentary adults begin an exercise program by starting at a level compatible with their current fitness (perhaps earning as few as 10 points per week for the first few weeks, for those at the lowest levels of fitness), choose an activity they enjoy, and exercise with others when at all possible. Table 2.1 provides examples of point values assigned to exercises by Cooper. Although neither Bowerman nor Cooper was able to base these recommendations on extensive bodies of directly relevant scientific evidence, both were talented practitioners and gifted communicators who were able to draw on their extensive experience in educating the public about how much physical activity is needed for health and fitness.
Exercise Prescription for the Public
Concurrent with the popularization of the exercise-for-fitness movement and the so-called running boom of the late 1960s and 1970s, exercise scientists began to systematically explore the effects of various types, intensities, durations, and frequencies of endurance exercise on cardiorespiratory fitness. A leader of this extensive scientific effort was Dr. Michael Pollock. During the 1970s, Pollock and his colleagues undertook a series of experimental exercise training studies that, when considered collectively along with the work of other researchers, produced the knowledge needed to recommend exercise in a precise, detailed, and individualized manner. This method became the central dogma in efforts to communicate to the public the types and amounts of exercise needed to promote health and fitness. The American College of Sports Medicine (ACSM) first formally endorsed this detailed approach to recommending exercise in its exercise guidelines book in 1975 (ACSM 1975) and in a position statement issued in 1978 (ACSM 1978). The key recommendations presented in the ACSM Position Statement are summarized in table 2.2.
During the same period in which exercise scientists were systematically studying endurance exercise training and its impact on cardiorespiratory fitness in healthy adults, cardiologists and clinical exercise physiologists were studying the effects of exercise training in patients with cardiovascular disease. This research demonstrated the critical and now well-accepted role that exercise can play in rehabilitation of patients with compromised cardiovascular function. But furthermore, this research and the clinical guidelines that it spawned established a medical approach to recommending exercise that came to be referred to as “exercise prescription.” This technique drew on the research on normal healthy adults as well as research performed on heart patients. In 1975, the AHA published guidelines on exercise prescription for patients with cardiovascular disease. This document helped to establish a place for exercise in the practice of medicine and was influential in communicating to the public the significant health benefits that accrue to physically active persons, even those with already established cardiovascular disease. Table 2.3 summarizes the AHA's first guidelines for physical activity in people with heart disease or at risk for heart disease (AHA 1975).
Importance of Moderate-Intensity Physical Activity
ACSM's Guidelines for Exercise Testing and Prescription has undergone revision approximately every five years since its initial publication in 1975 (ACSM 1975). Note that the first version of this was called Guidelines for Graded Exercise Testing and Prescription, but subsequent revisions dropped the word graded. Each volume included a primary recommendation on prescription of exercise that reflected the current body of knowledge regarding the types of exercise needed to provide health and fitness benefits to initially sedentary adults. Between the first edition published in 1975 and the eighth edition released in 2009, an interesting trend is evident. As shown by table 2.4, most elements in the exercise prescription guideline remained unchanged. The exception is the recommended range for exercise intensity, the lower end of which decreased from 60% .VO2max to 40%.VO2max. The earlier editions of this influential book indicated that rather vigorous exercise was needed to provide benefits, and this concept was widely communicated to the public during the 1970s and 1980s.
Recognition of the importance of moderate-intensity physical activity, as reflected by the changing exercise prescription guidelines of ACSM, evolved gradually during the 1980s and early 1990s as the result of a growing and changing body of research evidence. Two lines of research led to the conclusion that moderate-intensity physical activity (the equivalent of brisk walking) provided important benefits to health and fitness. First and most importantly, the science of physical activity epidemiology matured during the 1980s and produced a series of important investigations. These studies strongly suggested that regular performance of moderate-intensity physical activity provided important health benefits. Not only did these studies show that regularly active persons were less likely than sedentary persons to develop or die from cardiovascular disease, but they also demonstrated that much of the active population's physical activity came from walking and other forms of moderate-intensity physical activity. For example, results of the Third National Health and Nutrition Examination Survey (Crespo et al. 1996) showed that most of the physical activities preferred by American adults were moderate-intensity lifestyle activities, such as walking, gardening, and cycling (table 2.5).
As discussed previously, the exercise prescription method for recommending physical activity to the public was based primarily on the findings of a large number of experimental exercise training studies. The results of these studies had generally been interpreted as indicating that vigorous physical activity (6 METs or 60% or more individual functional capacity) was required to produce benefits. That moderate-intensity physical activity did not provide those benefits became the assumption. However, the epidemiological studies published in the 1980s and early 1990s forced a reexamination of the experimental studies. A closer look revealed that, in studies that compared moderate- and vigorous-intensity physical activity, the moderate level produced increased fitness, although often not to the same extent as the vigorous level. Also, it was seen that moderate-intensity physical activity often provided comparable or even greater beneficial effects on health outcomes such as blood pressure and high-density lipoprotein (HDL) cholesterol. For example, Duncan and colleagues (1991) found that both women who participated in a vigorous exercise program and those who participated in a moderate exercise program had significant improvements in their lipoprotein profiles (figure 2.3). Although women in the vigorous program had significantly greater gains in fitness, as measured by .VO2max, increases in HDL were similar in the two groups.
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Regular physical activity confers physiological, metabolic benefits
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity.
Research has repeatedly shown that exposure to regular, frequent bouts of physical activity stimulates physiological and metabolic changes that benefit health. It is helpful to classify these as either (a) chronic effects, that is, adaptations to training acquired over weeks or months, or (b) short-term, acute responses to each individual session of activity. Health-related adaptations to training are dealt with in other chapters. This chapter describes selected acute responses that are clearly related to health outcomes and explains their relevance. The extent to which these responses benefit health depends on the type, frequency, and regularity of activity and the extent to which particular acute responses persist into the postactivity period. For people who achieve the minimum recommended amounts of physical activity (Haskell et al. 2007, p. 1423), acute responses should be stimulated on five days per week (for moderate-intensity activity) or three days per week (for vigorous intensity). For reasons often related to statistical power and logistical considerations, the experimental models used to study acute health-related responses have relied mainly on planned, structured exercise, as opposed to physical activity performed during daily living. For this reason, the term exercise predominates in this chapter rather than physical activity. Studies of short periods of detraining are included because they illustrate that the changes to health outcomes that are rapidly lost when regular training is interrupted are mainly attributable to acute effects. Intuitively, unstructured periods of physical activity may be expected to stimulate acute responses that are qualitatively similar to, but less conspicuous than, those arising from planned sessions of exercise.
Lipids and Lipoproteins
Lipoproteins are particles that transport triglycerides and cholesterol in the blood plasma. They have a hydrophobic lipid core and an outer surface layer that allows the particle to mix with the watery plasma. Lipoproteins are classified according to their density, which in turn reflects their composition (see “Characteristics of the Main Classes of Lipoproteins”). There are clear links between markers for disordered lipoprotein metabolism and heart disease: Plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides are positively associated with the incidence of coronary heart disease, and there is a clear inverse relationship between high-density lipoprotein (HDL) cholesterol concentration and heart disease incidence. Changes to the concentration of lipoprotein lipids arising from a session of exercise are therefore of interest because of their implications for cardiovascular risk.
When considerable amounts of energy have been expended, changes to plasma concentrations of triglycerides, total cholesterol, or HDL cholesterol may be observed immediately after an exercise session. For example, men and women who completed the 1994 Hawaii Ironman Triathlon exhibited a nearly 40% decrease in triglycerides and decreases of around 10% in total and LDL cholesterol compared with prerace values. Events such as a marathon can result in an increase in HDL of about 10% after the race. These changes are independent of changes to plasma volume during these endurance events. On the other hand, a session of moderate-intensity exercise of relatively short duration does not lead to clear changes in lipoprotein variables measured immediately afterward. However, these measurements do not reveal the extent of the influence of such an exercise bout on lipoprotein metabolism.
Even a modest session of activity makes important inroads into the body's energy stores, leading to a prolonged period of metabolic “recovery.” Thus, when blood samples are obtained hours (rather than minutes) after exercise, effects on lipoprotein metabolism are clear. Decreases in triglycerides and increases in HDL cholesterol measured in the fasted state 24 h after a session of exercise have consistently been observed. The design of the HERITAGE Family Study was such that chronic adaptations to training could be distinguished from acute effects. In samples obtained 24 h following the last exercise session, researchers found that total cholesterol and very low-density lipoprotein (VLDL) triglycerides were lower after 20 weeks of training than at baseline, but there were no changes in samples obtained 72 h posttraining. In other words, these reductions were clearly acute responses to the last bout of exercise. The main factor influencing the extent of acute changes to triglycerides and HDL is the amount of energy expended during the exercise session, irrespective of exercise intensity. It may be that around 4.2 MJ (1,000 kcal or the equivalent of walking more than 16 km [10 mi]) need to be expended to elicit statistically significant changes.
These changes reflect the functional relationship that exists between plasma concentrations of triglycerides and HDL cholesterol. Hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL cholesterol) by the enzyme lipoprotein lipase (LPL) is accompanied by the transfer of cholesterol and other surface materials from triglyceride-rich particles into HDL. Thus, rapid removal of triglyceride-rich lipoproteins is associated with an increase in cholesterol carried in HDL. Prior exercise enhances triglyceride clearance rates, probably by increasing the activity of LPL in muscle—the rate-limiting step in triglyceride clearance. However, there appears to be little cumulative effect of repeated daily sessions of exercise on LPL activity, explaining why the decrease in triglycerides is essentially an acute effect of exercise that dissipates within 24 h.
Effect of Prior Exercise on Postprandial Triglycerides
Changes to lipoprotein metabolism after an exercise session therefore derive mainly from enhanced clearance of triglyceride-rich lipoproteins, a phenomenon most clearly seen when these particles are most numerous, that is, during the postprandial state. A rich body of data illustrates that prior exercise markedly decreases the triglyceride response to a subsequent meal. The clinical relevance of this is that an exaggerated postprandial triglyceride response has been linked to the presence of coronary artery disease and to the atherogenic lipoprotein phenotype. Moreover, people spend the majority of their lives in the postprandial state.
Figure 6.1 shows the effect of afternoon exercise (90 min at 60% of .VO2max) on serum triglyceride concentrations during the 6 h following a standard, high-fat meal consumed the following morning. The subjects were normally active (figure 6.1a) and endurance-trained (figure 6.1b) middle-aged women (Tsetsonis, Hardman, and Mastana 1997). Prior exercise decreased the postprandial response, measured as the area under the triglyceride concentration versus time curve, by 30% in trained women and by 16% in normally active women compared with values obtained in the control trial (no planned exercise for three days beforehand). Thus, a single session of exercise markedly decreases subsequent postprandial lipemia. This effect has been confirmed in various subject groups, including the obese. However, even in trained athletes, this effect is short-lived—and therefore an acute effect—as shown by a study of detraining. Endurance-trained athletes consumed a test meal on three occasions: 15 h, 60 h, and 6.5 days after their last training session. Compared with the 15-h value, the postprandial triglyceride response was 35% higher after just 60 h without exercise, with little further increase after nearly a week without training. Frequent exercise is therefore needed to maintain the cardiovascular benefits that may be assumed to arise from the triglyceride-lowering effects.
Influence of Intensity and Duration
Prior exercise has such a clear effect on postprandial triglycerides that this model has allowed investigation of the influence of exercise intensity (figure 6.2) and pattern (figure 6.3). Researchers examined the effect of the intensity of prior exercise (controlling for energy expenditure) using a repeated-measures design (Tsetsonis and Hardman 1996). The same participants consumed a high-fat, mixed meal on three occasions: (1) control, no planned exercise for three days beforehand; (2) 15 h after a 90-min treadmill walk at 60% .VO2max; and (3) 15 h after a walk that was twice as long (180 min) but at half the intensity (30% .VO2max). In other words, the researchers asked, “Can intensity be ‘traded' for duration?” As figure 6.2 clearly shows, the postprandial triglyceride response to dietary fat was decreased to the same degree (32%) after both exercise sessions, so the answer to this question (for this particular health outcome) is yes.
Different patterns of walking were compared in a study of daylong plasma triglyceride concentrations (figure 6.3). On three occasions, middle-aged participants were followed throughout a day during which they consumed three ordinary meals (Murphy, Nevill, and Hardman 2000). Compared with values from a control trial in which participants sat and worked quietly, plasma triglyceride concentrations were decreased to the same degree (12%) by either one 30-min walk before breakfast or by three 10-min walks taken before breakfast, lunch, and the early-evening meal. A subsequent study that compared the effect of 30 min of continuous walking with that of ten 3-min bouts reported strikingly similar findings (Miyashita, Burns, and Stensel 2008). Thus, the acute decrease in postprandial triglycerides attributable to exercise appears to be determined by the associated energy expenditure rather than by its intensity or pattern. Finally, there is evidence that the triglyceride-lowering effect of a bout of exercise extends into “real-world” settings where there may be a compensatory increase in food intake that reduces the net energy deficit attributable to the exercise bout (Farah, Malkova, and Gill 2010).
Endothelial Function
As mentioned previously, changes to lipoprotein metabolism during the hours after meal ingestion are likely to play an important role in the atherosclerotic disease process. However, the postprandial state is characterized also by nonlipid disturbances that are central to the progression of atherosclerosis.
Studies using a repeated-measures design have been employed to examine the effect of prior exercise on the postprandial impairment of endothelial function that persists for many hours after a high-fat meal. For example, using laser Doppler imaging of vasodilator responses to acetylcholine, researchers found that prior moderate exercise (90 min at 50% .VO2max) improved endothelium-dependent vasodilator function by an average of 15% over an 8-h postprandial period (Gill et al. 2004). This technique assesses the cutaneous microcirculation, regarded as a robust surrogate marker of vascular function in other vascular beds more directly involved in the pathogenesis of vascular diseases. Using a different technique, Tyldum and colleagues (2009) found significant attenuation by a single session of moderate exercise of the decrement in flow-mediated vasodilation of the brachial artery associated with a high-fat meal.
Improvements to endothelial function after a single exercise session appear therefore to be clearly discernable in small studies of apparently healthy subjects. Future repeated-measures studies to examine variables of duration, intensity, and pattern are feasible, as well as studies in groups that differ in clinical or training status. Complementary work will no doubt address the mechanisms by which exercise ameliorates postprandial impairment of vascular function: One possibility is a reduction by exercise of postprandial levels of oxidative stress.
Insulin-Glucose Dynamics
Insulin resistance is the main pathology of type 2 diabetes, and skeletal muscle is the body's largest insulin-sensitive tissue (see chapter 13). It is not surprising, therefore, that substrate deficits arising from a session of exercise influence whole-body insulin-glucose dynamics.
It has been known since the 1970s that endurance-trained individuals exhibit normal or improved glucose tolerance to a carbohydrate challenge despite a markedly reduced insulin response. More recently, a raft of detraining studies has shown that the improved insulin action underlying these characteristics is rapidly reversed with inactivity, suggesting that much of this benefit arises from acute rather than chronic effects. For example, King and colleagues investigated the effects of a seven-day interruption to training on glucose tolerance and insulin action (King et al. 1995). Participants were middle-aged individuals with a habit of regular moderate exercise, and the measures used were derived from a simple oral glucose tolerance test (OGTT) so as to reflect normal homeostatic mechanisms that pertain to real life. During the five days before these tests, participants performed 45 min of exercise daily at about 70% .VO2max. Glucose tolerance was poor immediately after the last exercise session, possibly because elevated plasma concentrations of nonesterified fatty acids inhibit glucose uptake into muscle, but had improved markedly 24 h later. This improved insulin action persisted for three days but not for five days, suggesting that the frequency of exercise needed to maintain the exercise-induced improvement in glucose tolerance is once every three days (figure 6.4). These findings were confirmed by the HERITAGE study of more than 500 previously sedentary men and women; 24 h after the last exercise bout of a 20-week training program, fasting insulin concentrations were lower than at pretraining, but this improvement was no longer evident 72 h after the last bout.
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Physical activity and weight loss: How much is enough
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide.
Role of Physical Activity in Prevention and Treatment of Excess Weight
From the preceding discussion, it is clear that a decrease in physical activity contributes to the increased prevalence of obesity worldwide. Accordingly, it is intuitive to suggest that an increase in physical activity levels would be associated with a decrease in obesity. Indeed, evidence from population-based studies with long-term follow-up confirms that age-related weight gain is attenuated in physically active adults compared with sedentary adults (Saris et al. 2003). However, while the experts agree that an increase in physical activity is associated with a lower prevalence of obesity, precisely how much physical activity is required to prevent age-related weight gain is the subject of considerable debate.
Physical activity guidelines for adults were initially formulated for the prevention of morbidity and mortality. Indeed, there is now a large body of evidence suggesting that the accumulation of 30 min or more of moderate-intensity physical activity on most days of the week provides substantial benefits across a broad range of health outcomes. Although 30 min of daily physical activity may prevent unhealthy weight gain in some individuals, it is now generally reported that this volume of physical activity may be insufficient for the prevention of the age-related weight gain in many if not most adults. Table 12.3 summarizes the reports from various expert groups that have considered how much physical activity is required to prevent weight gain. In general, the expert groups derived their recommendations from analysis of longitudinal, population-based studies that related estimates of self-reported physical activity levels over time to corresponding changes in body weight. The principal exception was the report from the Institute of Medicine, which based its recommendations on a cross-sectional analysis of data that used the doubly labeled water method to estimate total energy expenditure. Combined with the measurement of basal metabolic rate, the total energy expenditure values derived by doubly labeled water can be used to calculate an individual's physical activity level (PAL). The PAL is also used in population-based studies as a way of standardizing the various approaches used to determine physical activity energy expenditure. In short, the higher the PAL, the higher the level of physical activity performed on a daily basis.
The PAL is defined as the ratio of total energy expenditure to 24-h basal energy expenditure. Thus, PAL depends to a certain degree on body size and age, because these variables contribute to basal energy expenditure. Individuals can be placed into one of four activity categories based on their PAL, as shown in table 12.4.
The four PAL categories in the table correspond roughly to quartiles in the population. Thus, the Sedentary category is the lowest 25% of the population, whereas the Very Active category is the highest 25%. The Sedentary category was defined according to basal energy expenditure, the thermic effect of food, and the energy expended in physical activities that are required for independent living. Incorporating about 40 min per day of walking at a speed of 4.8 to 6.4 km/h (3 to 4 mph), in addition to the activities that are part of daily living, raises the PAL to the Low Active level in the average 70 kg (154 lb) person. To reach a PAL of 1.7 to 1.8—which is currently recommended for the prevention of age-related weight gain—the average 70 kg person must incorporate about 2 h per day of walking at 3 to 4 mph, in addition to the activities that are part of daily living.
The distances and times required to move to the more active categories vary considerably by body weight. Thus, more walking is required for lean individuals and less for obese individuals. People can reduce the times substantially by walking faster or performing other, more vigorous activities. For example, if the average person walked 30 min per day at 6.4 km/h (4 mph), cycled moderately for another 25 min, and played tennis for 40 min, the PAL would increase to about 1.75 (Active).
The consensus opinion at present is that the prevention of weight gain in both developed and undeveloped countries is associated with a PAL of about 1.7 to 1.8 (table 12.3). To achieve a PAL of 1.8 would require a physical activity habit equivalent to walking 8 to 11 km (5 to 7 mi) per day at 4.8 km/h (3 mph) in addition to the habitual activity required by a sedentary lifestyle. For most inactive people, this would require adding more than 60 min of physical activity to their daily routine.
On the other hand, the guidelines for prevention of weight gain have been derived in large measure from population-based cohorts of men and women, and thus the implementation of the guidelines may vary substantially among individuals. In other words, some people will maintain body weight by accumulating only 30 min of daily physical activity, whereas others may find it necessary to accumulate 60 to 120 min or more to maintain energy balance and to prevent weight gain. The point is that the quantity of physical activity required to maintain body weight (e.g., energy balance) varies depending on the individual. Also note that the guidelines for prevention of weight gain through physical activity are derived from studies that used primarily Caucasian adults. Accordingly, the potential influence of race on these guidelines is unknown.
On average, a PAL of about 1.75, which is equivalent to about 60 to 90 min of daily leisure-time physical activity, is recommended to prevent age-related weight gain.
Treatment of Obesity
The independent role of physical activity as a treatment strategy for obesity has received considerable attention. Early reviews of the literature suggested that the reduction in body weight (1-2 kg [2.2-4.4 lb]) associated with physical activity alone (e.g., no caloric restriction) was marginal, and thus physical activity in the absence of caloric restriction was not a particularly useful strategy for the treatment of obesity (NIH National Heart Lung and Blood Institute 1998). Subsequently, a careful inspection of the exercise studies revealed that, for the most part, few of the early studies prescribed an exercise program that would be expected to lead to meaningful weight loss (Ross and Janssen 2001). On the other hand, in studies in which the prescribed exercise program did result in a meaningful negative energy balance, weight loss was substantial (Ross and Janssen 2001). In other words, weight loss is positively related to the volume of physical activity performed. This point is illustrated in figure 12.4, showing a dose-response relationship between caloric expenditure and the time spent exercising with the corresponding reductions in body weight and total fat. However, daily exercise is not always associated with reductions in body weight or body fat. Some investigators report a resistance to weight loss in response to daily exercise performed for about 30 to 40 min for several months (Donnelly et al. 2003). Nevertheless, the majority of studies suggest that regular physical activity without restriction of caloric intake is associated with weight loss and a reduction in total fat in overweight men and women.
From figure 12.4, it is also clear that exercise performed for as little as 200 min per week is associated with weight loss. In fact, weight loss on the order of 0.5 kg (1 lb) per week is achieved in response to exercise performed for between 300 and 400 min per week or about 50 min per day. This observation is consistent with the position of the American College of Sports Medicine, which recommends that overweight and obese persons seeking weight loss should exercise between 200 and 300 min per week, the equivalent of about 8,374 J (2,000 kcal) per week (American College of Sports Medicine 2001).
Treatment of Abdominal Obesity
Whether an increase in physical activity is associated with a significant reduction in abdominal obesity is an important question. Minor reductions (~2 cm [~0.8 in.]) in waist circumference (a surrogate for abdominal fat) are observed in response to exercise-induced weight loss on the order of 2 to 3 kg (4.4-6.6 lb) (NIH National Heart Lung and Blood Institute 1998). In other words, similar to body weight, waist circumference is reduced a small amount in response to a small amount of physical activity. Although it is unclear whether a dose-response relationship exists between the amount of physical activity and the reduction in waist circumference, it is evident that larger reductions in waist circumference are observed in response to a significant amount of daily exercise. Indeed, exercise performed for 300 to 400 min per week, or about 60 min per day, is associated with reductions of about 0.5 cm per week. In fact, exercise performed for about 60 min per day for three to four months is associated with reductions in waist circumference that approach 5 to 6 cm (2-2.4 in.) in both men and women, as illustrated in figure 12.5.
Whether exercise-induced weight loss is associated with corresponding reductions in abdominal subcutaneous and visceral fat has also been considered (Ross and Janssen 2001). It is generally observed that exercise is associated with a substantial reduction in abdominal subcutaneous and visceral fat independent of gender and age. An example of this effect is shown in figure 12.6, where a 10% reduction in body weight is associated with a reduction in abdominal subcutaneous and visceral fat that approximates 25% and 35%, respectively. Figure 12.6 also shows that the greater the exercise level expressed in minutes per week, the greater the reduction in both abdominal subcutaneous and visceral fat.
Because visceral fat is such an important predictor of health risk, practitioners have questioned whether this fat depot is selectively reduced in response to exercise-induced weight loss. The answer depends on how the reduction is presented. That is, for a given weight loss, a greater reduction in abdominal subcutaneous fat is observed if the reduction is expressed in absolute values (e.g., cm2 at the L4-L5 image); the reason is that most adults have more abdominal subcutaneous fat than visceral fat. On the other hand, if the reduction in abdominal subcutaneous and visceral fat is expressed in relative terms (e.g., relative to the initial size of the depot), then the reduction in visceral fat is greater than the reduction in subcutaneous fat.
Exercise-Induced Reduction in Adiposity Without a Change in Body Weight
Emerging evidence suggests that regular exercise can reduce total and abdominal obesity in the absence of any change in body weight. This is supported by at least two lines of evidence. First, for any given level of BMI between 18 and 35 kg/m2, adults who are physically active (e.g., have a higher level of cardiorespiratory fitness) have a lower waist circumference and lower levels of abdominal subcutaneous and visceral fat compared with their sedentary counterparts (lower level of cardiorespiratory fitness) (Janssen et al. 2004). Second, results from well-controlled, randomized trials reveal that obese men and women who participate in exercise programs for three to four months can experience significant reductions in both waist circumference (figure 12.5) and abdominal subcutaneous and visceral fat despite no change in BMI (Ross et al. 2000, 2004). These observations are important because they suggest that those who seek obesity reduction by increasing physical activity should be educated about the possibility that reductions in waist circumference, total fat, and abdominal fat can occur with or without a corresponding weight loss. On the other hand, it is equally important to note that the reduction in both total and abdominal fat depots is much greater in response to exercise with weight loss than to exercise without weight loss (Ross and Bradshaw 2009). These observations highlight the importance of monitoring obesity reduction using both BMI and waist circumference.
Exercise in the absence of weight loss is associated with significant reductions in total, abdominal, and visceral fat in obese men and women. These reductions are, however, smaller than those associated with exercise-induced weight loss.
Summary
The prevalence of obesity is already high and is increasing worldwide. This poses a major threat to public health; and innovative, multidisciplinary strategies are required to combat the problem. The information presented in this chapter provides strong support for the recommendation that physical activity should be an integral component in the strategies developed to both prevent and treat the obesity epidemic. Current guidelines suggest that adults should accumulate about 60 min of moderate-intensity physical activity daily to prevent unhealthy weight gain. Results from shorter obesity treatment studies in which dietary intake was carefully controlled suggest that 60 min of moderate-intensity exercise without a change in energy intake is associated with substantial reductions in total and abdominal obesity in obese men and women.
Although it is now clear that an increase in daily physical activity is required for most individuals, the challenge that remains is how to engage in and maintain a physically active lifestyle. Increasing physical activity to the levels recommended for obesity prevention and reduction will require a multi-disciplinary approach that includes such components as educating allied health care providers about the benefits of physical activity, reestablishing daily physical education programs in our school systems, and working with urban planners to develop environments that encourage physical activity. Although the societal challenge to increase physical activity levels to an appropriate amount to combat the obesity epidemic is immense, the benefits are many, and thus the problem must be approached with vigor, step by step.
Key Concepts
abdominal subcutaneous fat—Layer of fat that lies directly underneath the skin in the abdominal region.
adipocyte—An adipose tissue or fat cell that stores lipids.
ad libitum—At one's pleasure; as one wishes.
body mass index (BMI)—A simple index of weight for height, calculated as weight in kilograms divided by the square of height in meters (kg/m2), that is commonly used to determine overweight and obesity status in research and clinical settings.
cytokines—For definition, see page 160.
ectopic fat—Fat that is stored outside of the adipose tissue depots.
lipolysis—Lipid breakdown reaction in adipocytes whereby the triglyceride molecule is hydrolyzed in the cell's cytosol into its components glycerol and three fatty acid molecules.
obesity—A condition of excessive fat accumulation to the extent that health may be impaired.
physical activity level (PAL)—Total daily caloric expenditure divided by total calories from resting metabolism. This term is being increasingly used as an overall indicator of energy expenditure.
visceral fat—Internal fat in the abdominal region that surrounds the organs of the gastrointestinal tract. Visceral fat consists of omental and mesenteric adipocytes and is contained within the visceral peritoneum.
waist circumference—A measurement of abdominal circumference commonly obtained at the top of the iliac crest. Waist circumference is used to characterize levels of abdominal obesity in research and clinical settings.
Study Questions
- What is BMI, how is it calculated, and what cut points are used to define overweight and obesity in adult men and women?
- List five major chronic diseases that are associated with obesity.
- Provide two examples of ectopic fat deposition in obesity, and explain their relationship to obesity-related disease.
- Describe how the average dietary intake, average leisure-time physical activity levels, and average total physical activity levels have changed in the past three decades and how these changes have contributed to the obesity epidemic.
- What is PAL, how is it calculated, and what levels are currently recommended for the prevention of unhealthy weight gain?
- What changes occur in abdominal subcutaneous and visceral fat in obese individuals in response to daily exercise performed for about 60 min at a moderate intensity?
- Discuss the importance of waist circumference in monitoring success in obesity reduction programs.
- What changes occur in waist circumference in response to exercise with or without weight loss?
References
American College of Sports Medicine. 2001. Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Medicine and Science in Sports and Exercise 33(12):2145-2156.
Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. 1990. Adrenergic regulation of lipolysis in situ at rest and during exercise. Journal of Clinical Investigation 85(3):893-898.
Björntorp, P. 1990. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10(4):493-496.
Blundell, J.E., R.J. Stubbs, D.A. Hughes, S. Whybrow, and N.A. King. 2003. Cross talk between physical activity and appetite control: Does physical activity stimulate appetite? Proceedings of the Nutrition Society 62(3):651-661.
Borghi, E., M. de Onis, C. Garza, J. Van den Broeck, E.A. Frongillo, L. Grummer-Strawn, S. Van Buuren, H. Pan, L. Molinari, R. Martorell, A.W. Onyango, and J.C. Martines. 2006. Construction of the World Health Organization child growth standards: Selection of methods for attained growth curves. Statistics in Medicine 25(2):247-265.
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