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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. Source

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. Source

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. Source

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. Source

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. Source

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