Physical Activity Following Surgery-Induced Weight Loss

摘要 肥胖和缺乏身体活动都与老年人死亡率和发病率的增加有关。 与2型糖尿病的发展风险增加相结合， 综合征和心血管疾病。我们建议检查身体活动是否会 在极高危人群中提供降低CVD风险因素的附加效应， 肥胖人群（非常肥胖的个体）接受减肥手术后。 我们每个研究小组的初步数据表明， 脂肪酸和减少氧化能力是密切相关的 肥胖胰岛素抵抗的病理生理学。从而损害脂肪酸的利用， 胰岛素抵抗都是肥胖症代谢不稳定的特征。的 普遍的观点是，线粒体功能障碍是代谢能力的基础 因此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，它做得很少，如果有的话，以改善 线粒体功能或促进肥胖症中脂肪酸的更有效利用。 此外，体力活动可能会促进对线粒体功能的积极影响， 酸代谢和胰岛素抵抗与体重减轻无关。 我们建议采用随机对照体力活动干预试验， 减肥手术后的一组患者。我们的主要假设是， 体重减轻+身体活动的组合将提供添加剂（并因此 独立的）积极影响：1）体重减轻和身体成分; 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;和3） 线粒体功能的标志物和肌肉有效利用脂肪的能力。 这些发现将是新颖的和相关的治疗肥胖，如病态肥胖 个体可能在遗传和环境上倾向于消极的 代谢状态和久坐不动的生活方式;体育活动是否能提供 对这些患者的体重急剧下降有额外的积极刺激。 调查手术减肥后增加体力活动的作用 对于我们理解治疗肥胖症的最有效策略及其 相关条件。因此，本研究产生的信息将有助于 确定最有效的治疗方法，以防止体重反弹，并改善 这些患者手术后的结果。项目叙述 肥胖和缺乏身体活动都与老年人死亡率和发病率的增加有关。 与2型糖尿病的发展风险增加相结合， 综合征和心血管疾病。我们建议检查身体活动是否会 在极高危人群中提供降低CVD风险因素的附加效应， 肥胖人群（非常肥胖的个体）接受减肥手术后。 我们每个研究小组的初步数据表明， 脂肪酸和减少氧化能力是密切相关的 肥胖胰岛素抵抗的病理生理学。从而损害脂肪酸的利用， 胰岛素抵抗都是肥胖症代谢不稳定的特征。的 普遍的观点是，线粒体功能障碍是代谢能力的基础 因此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，它做得很少，如果有的话，以改善 线粒体功能或促进肥胖症中脂肪酸的更有效利用。 此外，体力活动可能会促进对线粒体功能的积极影响， 酸代谢和胰岛素抵抗与体重减轻无关。 我们建议采用随机对照体力活动干预试验， 减肥手术后的一组患者。我们的主要假设是， 体重减轻+身体活动的组合将提供添加剂（并因此 独立的）积极影响：1）体重减轻和身体成分; 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;和3） 线粒体功能的标志物和肌肉有效利用脂肪的能力。 这些发现将是新颖的和相关的治疗肥胖，如病态肥胖 个体可能在遗传和环境上倾向于消极的 代谢状态和久坐不动的生活方式;体育活动是否能提供 对这些患者的体重急剧下降有额外的积极刺激。 调查手术减肥后增加体力活动的作用 对于我们理解治疗肥胖症的最有效策略及其 相关条件。因此，本研究产生的信息将有助于 确定最有效的治疗方法，以防止体重反弹，并改善 这些患者手术后的结果。

ABSTRACT 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. PROJECT NARRATIVE 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.