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且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，但很少有人能在很长一段时间内保持体重。这表明生理适应随着体重减轻而发生，反对进一步的体重减轻并促进体重恢复。体重减轻的状态与饮食相关激素反应的改变以及瘦素等长期肥胖信号有关，两者都可能促进能量摄入的增加。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，最终增加食物摄入。例如，在正常体重的个体中，环境食物相关线索和大脑区域之间似乎存在重要的相互作用，这些相互作用在食物摄入的稳态调节中很重要，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时发生了改变，在饮食引起的体重减轻后，这种变化更大，因为饮食引起的体重减轻有利于增加食物摄入量。这种无法适当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。虽然这两种干预都被证明与饮食相关激素反应的改变或“正常化”有关，这可能有利于减少食物摄入，但这些干预有助于促进体重减轻和防止体重反弹的机制尚不清楚。研究旨在阐明成功的减肥维持干预的机制，如这些是一个关键的研究领域。这项提议的总体目标是研究减肥手术和运动对神经元、行为和荷尔蒙对一顿饭的反应的影响。据推测，这些成功的减肥维持干预措施将恢复正常的神经元对饮食的反应，这种改善的神经元反应将与饮食相关激素和食欲评级的变化有关。为了检验这些假设，我们建议使用功能磁共振成像（fMRI）来检查饭前和饭后神经元对视觉食物线索的反应，以及研究接受Roux-en-Y胃分流术或胃束带的个体与饮食控制相比，以及通过监督运动干预保持体重减轻的个体与饮食控制相比，对进餐的激素反应。

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.