Physical Activity Following Surgery-Induced Weight Loss

描述（由申请人提供）：肥胖和缺乏身体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风险增加有关。我们建议研究在减肥手术后的极度危险人群（非常肥胖的个体）中，体育活动是否会提供降低心血管疾病危险因素的累加效应。我们每个研究小组的初步数据表明，脂肪酸的低效使用和氧化能力的降低与肥胖的胰岛素抵抗的病理生理密切相关。因此，脂肪酸利用受损和胰岛素抵抗都是肥胖代谢不灵活性的特征。普遍的范式是线粒体功能障碍支持代谢不灵活性，因此直接有助于骨骼肌胰岛素抵抗的病理生理。虽然这个假设很有吸引力，但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中脂肪酸的更有效利用几乎没有作用。此外，体育活动可能促进线粒体功能、脂肪酸代谢和胰岛素抵抗的积极作用，而不依赖于减肥。我们建议在减肥手术后的一组患者中采用随机对照体育活动干预试验。我们的主要假设是，减肥+体育活动的结合将提供附加的（因此是独立的）积极影响：1)减肥和身体组成；2)代谢危险因素如胰岛素作用等代谢综合征的标志物；3)线粒体功能和肌肉有效利用脂肪能力的标志物。这些发现将是新颖的，与治疗肥胖有关，因为病态肥胖的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；目前尚不清楚体育活动是否能对这些患者的显著体重减轻提供额外的积极刺激。研究手术减肥后增加体力活动的作用对我们了解治疗肥胖及其相关疾病的最有效策略至关重要。因此，从这项研究中获得的信息将有助于确定最有效的治疗方法，以防止体重反弹，并改善这些患者手术后的预后。

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.