Genetic Factors in Physical Activity and Obesity

描述（由申请人提供）：目前，美国超过一半的成年人被认为超重，这些成年人中几乎有四分之一达到或超过肥胖标准（BMI>30 kg/m2）。对相关和无关个体的大量研究为基因在决定身体大小和质量中的作用提供了支持。在病态肥胖的年轻人中尤其如此，在这些人中，肥胖的遗传易感性很可能先于或加剧这些个体中经常发现的暴饮暴食或缺乏体力活动的影响。旨在降低肥胖风险的预防计划通常侧重于可改变的环境和行为，如体育活动和饮食，个体之间的结果各不相同。这种对肥胖干预的异质性也至少部分是遗传起源。然而，很少有人知道与体重/脂肪和肥胖调节相关的基因中的遗传变异如何改变或影响一个人对运动或饮食干预的反应。虽然可能与肥胖相关的遗传因素的数量是相当大的，但至少有四种机制可能有助于个体的身体组成对运动干预的反应：1）脂肪组织形成和生长的倾向，2）肌肉细胞生长或维持的倾向，3）对影响饱腹感的因素的敏感性，和/或4）能量代谢的改变。因此，本研究的目的是调查与脂肪形成，肌细胞分化和生长，饱腹感和能量代谢相关的基因内的遗传变异与对一个完善的30周运动训练方案的反应之间的关联，通过身体成分和血脂的变化来确定，在多种族的大学年龄男性和女性队列中。此外，我们还将研究训练前和训练后脂肪和肌肉组织样本中的基因表达水平，以确定与身体成分和/或运动反应性相关的其他基因。我们从多个种族群体中选择了一个强大的男性和女性样本（N= 1，536），旨在最大限度地提高我们检测与身体成分变化相关的遗传差异的可能性。这项研究的结果将是非常宝贵的，不仅在了解运动反应和身体成分变化的过程，而且在改善干预计划，旨在减少或预防肥胖。

DESCRIPTION (provided by applicant): Currently, more than half the adults in the U.S. are considered to be overweight, and almost one quarter of these adults meet or surpass the criteria for obesity (BMI>30 kg/m2). Numerous studies of related and unrelated individuals have provided support for the role of genes in the determination of body size and mass. This is particularly true in the case of morbidly obese young adults, in whom a genetic susceptibility for obesity very likely precedes or exacerbates the effects of overeating or lack of physical activity often found in these individuals. Prevention programs designed to reduce the risk of obesity commonly focus on modifiable environments and behaviors such as physical activity and diet, with varied results among individuals. This heterogeneity in response to obesity interventions is also at least in part of genetic origin. Nevertheless, little is known about how genetic variation in genes related to the regulation of body mass/fat and obesity may alter or influence one's response to exercise or diet intervention. Though the number of genetic factors that may be related to obesity is substantial, at least four mechanisms may contribute to an individual's body composition response to exercise intervention: 1) predisposition for the formation and growth of adipose tissue, 2) propensity for muscle cell growth or maintenance, 3) sensitivity to factors that influence satiety, and/or 4) alterations in energy metabolism. Thus, the purpose of this study is to investigate the association between genetic variation within genes related to adipogenesis, myocyte differentiation and growth, satiety, and energy metabolism and response to a well-established 30-week exercise training protocol, as determined by changes in body composition and blood lipids, in a multi-racial cohort of college-age men and women. In addition, we will investigate levels of gene expression in adipose and muscle tissue samples both pre- and post-training in order to identify additional genes related to body composition and/or responsivity to exercise. We have selected a powerful sample of males and females from multiple racial groups (N=1,536) designed to maximize our likelihood of detecting genetic differences related to body composition change. Results of this study will be invaluable not only in understanding the processes of exercise response and body composition change but also in improving intervention programs designed to reduce or prevent obesity.