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Bouchard C.,Pennington Biomedical Research Center
Exercise and Sport Sciences Reviews | Year: 2011

This commentary focuses on the issues of statistical power, the usefulness of hypothesis-free approaches such as in genome-wide association explorations, the necessity of expanding the research beyond common DNA variants, the advantage of combining transcriptomics with genomics, and the complexities inherent to the search for links between genotype and phenotype in exercise genomics research. © 2011 by the American College of Sports Medicine.


Stadler K.,Pennington Biomedical Research Center
Advances in experimental medicine and biology | Year: 2012

Oxidative stress and diabetes, both Type 1 and Type 2 as well as their related conditions have been extensively studied. As diabetes, obesity and metabolic syndrome have reached at epidemic levels, there is a huge need and effort to understand the detailed molecular mechanisms of the possible redox imbalance, underlying the cause of pathology and progression of the disease. These studies provide new insights at cellular and subcellular levels to design effective clinical interventions. This chapter is intended to emphasize the latest knowledge and current evidence on the role of oxidative stress in diabetes as well as to discuss some key questions that are currently under discussion.


Bouchard C.,Pennington Biomedical Research Center
Experimental Physiology | Year: 2012

The concept of individual differences in the response to exercise training or trainability was defined three decades ago. In a series of experimental studies with pairs of monozygotic twins, evidence was found in support of a strong genotype dependency of the ability to respond to regular exercise. In the HERITAGE Family Study, it was observed that the heritability of the maximal oxygen uptake response to 20 weeks of standardized exercise training reached 47% after adjustment for age, sex, baseline maximal oxygen uptake and baseline body mass and composition. Candidate gene studies have not yielded as many validated gene targets and variants as originally anticipated. Genome-wide explorations have generated more convincing predictors of maximal oxygen uptake trainability. A genomic predictor score based on the number of favourable alleles carried at 21 single nucleotide polymorphisms appears to be able to identify low and high training response classes that differ by at least threefold. Combining transcriptomic and genomic technologies has also yielded highly promising results concerning the ability to predict trainability among sedentary people. © 2012 The Author. Journal compilation © 2012 The Physiological Society.


Katzmarzyk P.T.,Pennington Biomedical Research Center
Medicine and Science in Sports and Exercise | Year: 2014

PURPOSE: Several studies have documented significant associations between sedentary behaviors such as sitting or television viewing and premature mortality. However, the associations between mortality and other low-energy-expenditure activities such as standing have not been explored. The purpose of this study was to examine the association between daily standing time and mortality among 16,586 Canadian adults 18-90 yr of age. METHODS: Information on self-reported time spent standing as well as several covariates including smoking, alcohol consumption, physical activity readiness, and moderate-to-vigorous physical activity was collected at baseline in the 1981 Canada Fitness Survey. Participants were followed for an average of 12.0 yr for the ascertainment of mortality status. RESULTS: There were 1785 deaths (743 from cardiovascular disease [CVD], 530 from cancer, and 512 from other causes) in the cohort. After adjusting for age, sex, and additional covariates, time spent standing was negatively related to mortality rates from all causes, CVD, and other causes. Across successively higher categories of daily standing, the multivariable-adjusted hazard ratios were 1.00, 0.79, 0.79, 0.73, and 0.67 for all-cause mortality (P for trend <0.0001); 1.00, 0.82, 0.84, 0.68, and 0.75 for CVD mortality (P for trend 0.02); and 1.00, 0.76, 0.63, 0.67, and 0.65 for other mortality (P for trend <0.001). There was no association between standing and cancer mortality. There was a significant interaction between physical activity and standing (P < 0.05), and the association between standing and mortality was significant only among the physically inactive (<7.5 MET·h·wk). CONCLUSIONS: The results suggest that standing may not be a hazardous form of behavior. Given that mortality rates declined at higher levels of standing, standing may be a healthier alternative to excessive periods of sitting. © 2014 by the American college of Sports Medicine.


Munzberg H.,Pennington Biomedical Research Center
Forum of Nutrition | Year: 2010

Leptin acts as an anorexigenic hormone in the brain, where the long form of the leptin receptor (LRb) is widely expressed in hypothalamic and extra-hypothalamic sites that are known to participate in diverse feeding circuits. The important role of leptin in energy homeostasis is demonstrated by the profound hyperphagia and morbid obesity in humans and rodents null for leptin or LRb. However, common forms of obesity are associated with high leptin levels and a failure to respond effectively to exogenous leptin; indicating a state of leptin resistance. Leptin resistance is thought to be an important component in the development of obesity. Several defects may contribute to the leptin resistant state, including a defective leptin transport across the blood-brain barrier, which reduces the availability of leptin at its receptor. Furthermore, defects in LRb signal transduction involving reduced LRb expression or the induction of feedback inhibitors have been found in leptin resistance; these defects are commonly termed cellular leptin resistance,. Finally, reduced leptin action can result in the disruption of proper neuronal interactions, by altering neuronal wiring. Interestingly, some leptin functions remain intact in the leptin-resistant state, such as cardiovascular leptin effects. The appearance of selective leptin resistance is mirrored by the observation that cellular leptin resistance has been found only in some subpopulations of hypothalamic LRb neurons. Current efforts to dissect leptin function in specific populations of LRb neurons will increase our understanding of these complexities of leptin physiology. Copyright © 2010 S. Karger AG, Basel.


Tudor-Locke C.,Pennington Biomedical Research Center
Journal of physical activity & health | Year: 2011

The purpose of this review is to update the methodological aspects of pedometry to encourage the consistent use of pedometers for assessment, to decrease sources of error, and to facilitate comparison and interpretation of results. The specific measurement topics addressed include: instrument choice, metric choice, validity, reliability, data collection and retrieval, time worn, day-to-day variability, monitoring time frame, reactivity, and data treatment. A wide variety of valid and reliable instruments are commercially available and we can expect continued evolutions in value-added features as supporting technology improves. Data collection and retrieval has been achieved through various methods, including face-to-face contact, fax, e-mail, website, and conventional mail, and sometimes a combination of these. Day-to-day variation is not random, as would be expected from inconsistent pedometer performance, but rather exposes true behavior instability that can be explained by other factors and described using a coefficient of variation. Data reduction should be conducted cautiously and only after a full discovery (and disclosure) of its impact on aggregated group statistics and their relationship with other parameters. We have no doubt that research with pedometers will continue to yield new and important insights in the coming years.


Staiano A.E.,Pennington Biomedical Research Center
International journal of obesity (2005) | Year: 2012

Body fat and the specific depot where adipose tissue (AT) is stored can contribute to cardiometabolic health risks in children and adolescents. Imaging procedures including magnetic resonance imaging and computed tomography allow for the exploration of individual and group differences in pediatric adiposity. This review examines the variation in pediatric total body fat (TBF), visceral AT (VAT) and subcutaneous AT (SAT) due to age, sex, maturational status and ethnicity. TBF, VAT and SAT typically increase as a child ages, though different trends emerge. Girls tend to accumulate more TBF and SAT during and after puberty, depositing fat preferentially in the gynoid and extremity regions. In contrast, pubertal and postpubertal boys tend to deposit more fat in the abdominal region, particularly in the VAT depot. Sexual maturation significantly influences TBF, VAT and SAT. Ethnic differences in TBF are mixed. VAT tends to be higher in white and Hispanic youth, whereas SAT is typically higher in African American youth. Asian youth typically have less gynoid fat but more VAT than whites. Obesity per se may attenuate sex and ethnic differences. Particular health risks are associated with high amounts of TBF, VAT and SAT, including insulin resistance, hepatic steatosis, metabolic syndrome and hypertension. These risks are affected by genetic, biological and lifestyle factors including physical activity, nutrition and stress. Synthesizing evidence is difficult as there is no consistent methodology or definition to estimate and define depot-specific adiposity, and many analyses compare SAT and VAT without controlling for TBF. Future research should include longitudinal examinations of adiposity changes over time in representative samples of youth to make generalizations to the entire pediatric population and examine variation in organ-specific body fat.


Bray G.A.,Pennington Biomedical Research Center
Obesity | Year: 2013

Objective: Obesity is a public health problem, which increases the risk of chronic diseases and mortality. Weight loss can reduce mortality and improve most of the detrimental health consequences of obesity. Design and Methods: This paper was developed from two presentations to the US Food and Drug Administration (FDA), which has responsibility for reviewing and approving drugs to treat obesity. Results: A weight loss of 5% or more is sufficient to significantly reduce health risks in individuals with impaired glucose tolerance, hypertension, or nonalcoholic fatty liver disease. Slightly more weight loss (16% on average, achieved by surgery) reduces mortality. The goal of medicating for obesity is to help more patients achieve more weight loss. A barrier to drug approval has been the concern that weight loss medications might be used by individuals with little or no health risks, thus mandating a low side effect profile for approval of any drug. This limits the options for patients who have obesity-related health problems that could improve with weight loss. Recently the FDA signaled interest in identifying health benefits in higher risk patients that might justify medications with higher risk; however, the potential impact on a large segment of the population has led the FDA to consider requiring a cardiovascular outcome trial for all obesity medications, either prior to or after approval. Conclusion: This review argues that drugs are needed for obesity because they enhance behaviorally induced weight loss and that new medications for obesity are needed in the approval process. Copyright © 2013 The Obesity Society.


Ravussin E.,Pennington Biomedical Research Center | Galgani J.E.,University of Chile
Annual Review of Nutrition | Year: 2011

We here discuss the role of brown adipose tissue on energy homeostasis and assess its potential as a target for body weight management. Because of their high number of mitochondria and the presence of uncoupling protein 1, brown fat adipocytes can be termed as energy inefficient for adenosine-5′- triphosphate (ATP) production but energy efficient for heat production. Thus, the energy inefficiency of ATP production, despite high energy substrate oxidation, allows brown adipose tissue to generate heat for body temperature regulation. Whether such thermogenic property also plays a role in body weight regulation is still debated. The recent (re)discovery of brown adipose tissue in human adults and a better understanding of brown adipose tissue development have encouraged the quest for new alternatives to treat obesity since obese individuals seem to have less brown adipose tissue mass/activity than do their lean counterparts. In this review, we discuss the physiological relevance of brown adipose tissue on thermogenesis and its potential usefulness on body weight control in humans. Copyright © 2011 by Annual Reviews. All rights reserved.


Kushner R.F.,Northwestern University | Ryan D.H.,Pennington Biomedical Research Center
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE: Even though one-third of US adults are obese, identification and treatment rates for obesity remain low. Clinician engagement is vital to provide guidance and assistance to patients who are overweight or obese to address the underlying cause of many chronic diseases. OBJECTIVES: To describe current best practices for assessment and lifestyle management of obesity and to demonstrate how the updated Guidelines (2013) for Managing Overweight and Obesity in Adults based on a systematic evidence review sponsored by the National Heart, Lung, and Blood Institute (NHLBI) can be applied to an individual patient. EVIDENCE REVIEW: Systematic evidence review conducted for the Guidelines (2013) for Managing Overweight and Obesity in Adults supports treatment recommendations in 5 areas (risk assessment, weight loss benefits, diets forweight loss, comprehensive lifestyle intervention approaches, and bariatric surgery); for areas outside this scope, recommendations are supported by other guidelines (for obesity, 1998 NHLBI-sponsored obesity guidelines and those from the National Center for Health and Clinical Excellence and Canadian and US professional societies such as the American Association of Clinical Endocrinologists and American Society of Bariatric Physicians; for physical activity recommendations, the 2008 Physical Activity Guidelines for Americans); a PubMed search identified recent systematic reviews covering depression and obesity, motivational interviewing forweight management, metabolic adaptation toweight loss, and obesity pharmacotherapy. FINDINGS: The first step in obesity management is to screen all adults for overweight and obesity. A medical history should be obtained assessing for the multiple determinants of obesity, including dietary and physical activity patterns, psychosocial factors, weight-gaining medications, and familial traits. Emphasis on the complications of obesity to identify patients who will benefit the most from treatment is more useful than using body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) alone for treatment decisions. The Guidelines (2013) recommend that clinicians offer patients who would benefit from weight loss (either BMI of ≥30 with or without comorbidities or ≥25 along with 1 comorbidity or risk factor) intensive, multicomponent behavioral intervention. Some clinicians do this within their primary care practices; others refer patients for these services. Weight loss is achieved by creating a negative energy balance through modification of food and physical activity behaviors. The Guidelines (2013) endorse comprehensive lifestyle treatment by intensive intervention. Treatment can be implemented either in a clinician's office or by referral to a registered dietitian or commercial weight loss program. Weight loss of 5%to 10% is the usual goal. It is not necessary for patients to attain a BMI of less than 25 to achieve a health benefit. CONCLUSIONS AND RELEVANCE Screening and assessment of patients for obesity followed by initiation or referral of treatment should be incorporated into primary care practice settings. If clinicians can identify appropriate patients for weight loss efforts and provide informed advice and assistance on how to achieve and sustain modest weight loss, they will be addressing the underlying driver of many comorbidities and can have a major influence on patients' health status. Copyright 2014 American Medical Association. All rights reserved.

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