Neuronal Responses to Effective Weight Loss Maintenance Strategies

描述（由申请人提供）：肥胖是美国和世界上一个严重的和日益严重的公共卫生问题。虽然许多超重和肥胖的人可以减肥，但很少有人能在相当长的一段时间内保持减肥。这表明，生理适应发生与体重减轻，反对进一步减肥，促进体重反弹。体重减轻状态与膳食相关的激素反应以及长期肥胖信号（如瘦素）的改变有关，两者都可能促进能量摄入增加。虽然这些信号可能直接影响能量平衡调节，但越来越多的证据表明，这些生理信号与奖励，行为和认知系统相互作用，最终提高食物摄入量。例如，在正常体重的个体中，环境食物相关的线索和已知在食物摄入的稳态调节中重要的大脑区域之间似乎存在重要的相互作用，并且这些相互作用受到食物摄入和能量平衡的影响。这些反应似乎在肥胖症中发生了改变，在饮食诱导的体重减轻后更是如此，这将有利于增加食物摄入。这种不能适当地适应环境可能是长期减肥难以成功维持的重要机制。因此，成功的减肥维持干预措施必须通过生理和非生理系统之间复杂的相互作用来控制能量平衡，了解这些机制将有助于开发新的和/或更好的减肥维持策略。两种成功的干预措施是减肥手术和锻炼。虽然这两种干预措施已被证明与饮食相关的激素反应的变化或“正常化”有关，可能有利于减少食物摄入量，但这些干预措施有助于促进减肥和防止体重反弹的机制尚不清楚。旨在阐明成功减肥维持干预措施的机制的研究，如这些是一个关键的调查领域。这项提案的总体目标是研究减肥手术和运动对神经元，行为和激素反应的影响。假设这些成功的体重减轻维持干预将恢复对膳食的正常神经元反应，并且这种改善的神经元反应将与膳食相关激素和食欲等级的变化相关。为了检验这些假设，我们建议使用功能磁共振成像检查神经元的反应，以视觉食物线索之前和之后的一餐，以及研究激素反应的一餐在个人谁经历了Roux-en-Y胃旁路或胃束带相比，饮食控制和个人保持体重减轻，通过监督运动干预相比，饮食控制。 公共卫生相关性：肥胖是美国和世界上一个严重的和日益严重的公共卫生问题。虽然许多超重和肥胖的人可以减肥，但很少有人能在相当长的一段时间内保持减肥。这表明，适应发生与体重减轻，反对进一步减肥，促进体重反弹。持续减肥最成功的干预措施是减肥手术和运动。然而，目前尚不清楚这些干预措施如何帮助个人保持体重减轻。通过了解大脑对进食和食物线索的反应与这些干预措施的生理变化之间的复杂相互作用，我们希望能够开发新的策略和/或干预措施来持续减肥。

DESCRIPTION (provided by applicant): Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that physiological adaptations occur with weight loss that oppose further weight loss and promote weight regain. The weight reduced state is associated with alterations in meal-related hormone responses as well as long-term adiposity signals such as leptin both potentially promoting increased energy intake. While these signals may directly impact energy balance regulation, there is increasing evidence that these physiologic signals interact with reward, behavioral and cognitive systems to ultimately enhance food intake. For example, in normal weight individuals, there appear to be important interactions between environmental food-related cues and brain regions known to be important in the homeostatic regulation of food intake, and these interactions are affected by food intake and energy balance. These responses appear to be altered in obesity and more so following diet-induced weight loss which would favor increase food intake. This inability to properly adapt to the environment may represent an important mechanism for the difficulty of successful long-term weight loss maintenance. Successful weight loss maintenance interventions must, therefore, require control of energy balance via a complex interaction between physiologic and nonphysiologic systems, and understanding these mechanisms will allow for the potential development of new and/or better strategies for weight loss maintenance. Two such successful interventions are weight loss surgery and exercise. While both of these interventions have been shown to been associated with changes or 'normalization' in meal-related hormone responses that might favor reduced food intake, the mechanisms by which these interventions help promote weight loss and prevent weight regain are not well understood. Studies designed to elucidate the mechanisms of successful weight loss maintenance interventions such as these are a critical area for investigation. The overall goal of this proposal is to examine the effects of weight loss surgery and exercise on the neuronal, behavioral and hormonal response to a meal. It is hypothesized that these successful weight loss maintenance interventions will restore the normal neuronal response to a meal and that this improved neuronal response will be associated with changes in both meal associated hormones and appetite ratings. In order to examine these hypotheses we propose to use fMRI to examine the neuronal response to visual food cues before and after a meal as well as to study the hormonal response to a meal in individuals who have undergone Roux-en-Y gastric bypass or gastric banding as compared to diet control and in individuals maintaining weight loss through a supervised exercise intervention as compared to diet control. PUBLIC HEALTH RELEVANCE: Obesity is a serious and growing public health problem in the United States and the world. While many overweight and obese individuals can lose weight, few can maintain weight loss for substantial periods of time. This suggests that adaptations occur with weight loss that oppose further weight loss and promote weight regain. The most successful interventions for sustained weight loss are bariatric surgery and exercise. It is unclear, however, how these interventions help individuals maintain a reduced body weight. By understanding the complex interactions between the brain response to eating and food cues and physiologic changes with these interventions we hope to be able to develop new strategies and/or interventions for sustained weight loss.