Exercise training and insulin resistance in overweight children and adolescents

描述（由申请人提供）：美国的儿童和青少年继续比上一代的父母吃得更多，锻炼得更少；这种营养过剩和缺乏运动的结合在一定程度上要归咎于肥胖的流行，这可能会缩短年轻人的预期寿命。许多肥胖的不良后遗症是由胰岛素抵抗介导的。了解如何在这一脆弱人群中逆转与肥胖相关的胰岛素抵抗具有重要的公共卫生意义。本研究是一项随机对照试验，旨在评估有监督的居家8周运动训练干预对超重儿童和青少年胰岛素抵抗的影响，并探讨与健身相关的胰岛素抵抗改善可能发生的机制。具体来说，我们假设运动可以改变骨骼肌的生理机能，从而改善胰岛素敏感性。瘦肉量、线粒体功能和细胞内脂质含量是骨骼肌水平胰岛素抵抗的候选调节剂，可能受到运动的影响；我们将研究这些因素对运动相关胰岛素敏感性变化的潜在影响。最后，为了支持和扩展我们的发现，我们建议同时测量许多代谢物（氨基酸、糖、低分子量脂类）的浓度。我们希望确定其他可以通过运动改变的生物学途径，并与更好的胰岛素敏感性相关，这可能是未来工作的重点。更好地了解运动是如何改善胰岛素抵抗的，可以揭示这种疾病的发病机制，并为患者提供更有效的运动处方。

DESCRIPTION (provided by applicant): Children and adolescents in the United States continue to eat more and exercise less than their parents did a generation ago; this combination of overnutrition and inactivity is partly to blame for an epidemic of obesity that threatens to shorten life expectancy of young people. Many of the adverse sequelae of obesity are mediated by insulin resistance. Understanding how to reverse obesity-associated insulin resistance in this vulnerable population is of critical public health importance. The proposed study is a randomized controlled trial to evaluate the impact of a supervised in-home 8-week exercise training intervention on insulin resistance in overweight children and adolescents, and to explore the mechanisms by which fitness-related amelioration of insulin resistance may occur. Specifically, we hypothesize that exercise will produce alterations in skeletal muscle physiology that will improve insulin sensitivity. The amount of lean mass, mitochondrial function, and intramyocellular lipid content are candidate modulators of insulin resistance at the level of the skeletal muscle that may be affected by exercise; we will investigate the potential contribution of each of these to exercise- related changes in insulin sensitivity. Finally, to support and extend our findings, we propose to simultaneously measure the concentrations of many metabolites (amino acids, sugars, low molecular weight lipids). We hope to identify other biological pathways modifiable by exercise and associated with better insulin sensitivity that can be the focus of future work. A better understanding of how exercise may ameliorate insulin resistance could shed light on pathogenesis of this condition and lead to more effective exercise prescriptions for patients. PUBLIC HEALTH RELEVANCE: Children and adolescents in the United States continue to eat more and exercise less than their parents did a generation ago; this combination of excess nutrition and inactivity is partly to blame for an epidemic of obesity that threatens to shorten life expectancy of young people. We propose a study to evaluate whether exercise can reverse some of the harmful effects of obesity in this important population, and if so, how it might work. We hope that a better understanding of how exercise helps will lead to insights into obesity and its consequences in children and adolescents, as well as more effective exercise prescriptions for our pediatric patients.