Physical Activity Following Surgery-Induced Weight Loss

描述（由申请人提供）：肥胖和缺乏身体活动均与死亡率和发病率增加以及2型糖尿病、代谢综合征和心血管疾病发生风险增加相关。我们建议检查，如果体力活动将提供一个附加效应，减少危险因素的心血管疾病在一个极端的风险人群（非常肥胖的人）减肥手术后。来自我们每个研究小组的初步数据表明，脂肪酸的低效利用和氧化能力的降低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症代谢紊乱的特征。普遍的范式是线粒体功能障碍支持代谢的稳定性，从而直接导致骨骼肌胰岛素抵抗的病理生理学。虽然这一假设很有吸引力，但尚未得到实验证明。虽然减肥本身可以改善胰岛素抵抗，但它几乎没有改善线粒体功能或促进肥胖症中脂肪酸的更有效利用。此外，体力活动可以促进对线粒体功能、脂肪酸代谢和胰岛素抵抗的积极影响，而不依赖于体重减轻。我们建议在一组减肥手术后的患者中进行随机对照的体力活动干预试验。我们的主要假设是，体重减轻+体力活动的组合将对以下方面产生叠加（因此是独立的）积极影响：1）体重减轻和身体组成; 2）代谢风险因素，如胰岛素作用和代谢综合征的其他标志物; 3）线粒体功能标志物和肌肉有效利用脂肪的能力。这些发现将是新颖的，并与治疗肥胖相关，因为病态肥胖个体可能在遗传和环境上倾向于负代谢状态和久坐不动的生活方式;体育活动是否能为这些患者的体重急剧减轻提供额外的积极刺激尚不明显。调查手术引起的体重减轻后增加身体活动的作用对于我们理解治疗肥胖及其相关疾病的最有效策略至关重要。因此，本研究的信息将有助于确定最有效的治疗方法，以防止体重反弹，并改善这些患者术后的结局。

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.