Physical Activity Following Surgery-Induced Weight Loss

描述(申请人提供)：肥胖和缺乏体力活动都与死亡率和发病率的增加有关，同时也与2型糖尿病、代谢综合征和心血管疾病的发展风险增加有关。我们建议检验体育锻炼是否会在减肥手术后的极高风险人群(非常肥胖的个体)中提供减少心血管疾病危险因素的附加效应。来自我们每个研究小组的初步数据表明，低效率地使用脂肪酸和氧化能力减弱与肥胖的胰岛素抵抗的病理生理学密切相关。因此，脂肪酸利用受损和胰岛素抵抗都是肥胖患者代谢不灵活的特征。普遍认为线粒体功能障碍是代谢不灵活的基础，因此直接导致骨骼肌胰岛素抵抗的病理生理学过程。尽管这一假设很有吸引力，但它还没有得到实验证明。虽然减肥本身可以改善胰岛素抵抗，但它对改善线粒体功能或促进肥胖患者更有效地利用脂肪酸几乎没有作用。此外，体育活动可能会促进对线粒体功能、脂肪酸代谢和胰岛素抵抗的积极影响，而不是与体重减轻无关。我们建议在减肥手术后的一组患者中采用随机对照体力活动干预试验。我们的主要假设是，减肥和体力活动的结合将在以下方面提供相加的(因此也是独立的)积极影响：1)减肥和身体成分；2)代谢风险因素，如胰岛素作用和其他代谢综合征标记物；3)线粒体功能和肌肉有效利用脂肪能力的标记物。这些发现将是治疗肥胖症的新发现，并与治疗肥胖症相关，因为病态肥胖者可能在基因和环境上倾向于负代谢状态和久坐不动的生活方式；目前尚不清楚体育活动是否能为这些患者的显著减肥提供额外的积极刺激。研究手术减肥后体力活动增加的作用，对于我们理解治疗肥胖症及其相关疾病的最有效策略至关重要。因此，这项研究的信息将有助于确定最有效的治疗方法来防止体重回升，并改善这些患者手术后的结果。

DESCRIPTION (provided by applicant): Obesity and physical inactivity are both related to increased mortality and morbidity in conjunction with increased risk for the development of type 2 diabetes, the metabolic syndrome and cardiovascular disease. We propose to examine if physical activity will provide an additive effect of reducing risk factors for CVD in an extremely at risk population (very obese individuals) following bariatric weight loss surgery. Preliminary data from each of our research groups has indicated that an inefficient use of fatty acids and diminished oxidative capacity is strongly associated with the pathophysiology of insulin resistance of obesity. Thus impaired fatty acid utilization and insulin resistance are both characteristic of the metabolic inflexibility in obesity. The prevailing paradigm is that mitochondrial dysfunction underpins metabolic inflexibility and thus directly contributes to the pathophysiology of skeletal muscle insulin resistance. While this hypothesis is attractive, it has not been experimentally proven. Although weight loss itself can improve insulin resistance, it does little, if anything to improve mitochondria function or to promote more efficient utilization of fatty acids in obesity. Moreover, physical activity may promote positive effects on mitochondria function, fatty acid metabolism and insulin resistance independent of weight loss. We propose to employ a randomized controlled physical activity intervention trial in a group of patients following their weight loss surgery. Our primary hypotheses are that the combination of weight loss + physical activity will provide additive (and thus independent) positive effects on: 1) weight loss and body composition; 2) metabolic risk factors such as insulin action and other markers of the metabolic syndrome; and 3) markers of mitochondria function and the capacity for efficient fat utilization by muscle. These findings will be novel and relevant to treating obesity, as morbidly obese individuals are likely genetically and environmentally predisposed towards a negative metabolic status and a sedentary lifestyle; it is not evident if physical activity can provide an additional positive stimulus to dramatic weight loss in these patients. Investigating the role of increased physical activity following surgery-induced weight loss is critical to our understanding of the most effective strategies to treat obesity and its associated conditions. Information emanating from this study would thus help to determine the most effective treatments to prevent weight regain and to improve outcomes of these patients following surgery.