Neurohormonal and Behavioral Correlates of Obesity and Weight Loss

描述（由申请人提供）：肥胖在美国已经达到流行病的水平。长期减肥的累犯率是相当大的，并提出了一个关键问题，因为肥胖作为2型糖尿病等疾病的可改变风险因素的重要性。该K 01指导研究科学家奖将支持候选人建立独立的研究生涯，使用纵向心理行为测试和神经成像来调查中枢阿片系统反应在肥胖中的作用。该应用程序的培训部分建立在候选人的运动科学和行为神经科学背景，同时提供了一个独特的视角来研究肥胖的病理生理学。 研究部分将检查瘦个体和肥胖个体在减肥前后的心理行为（冲动控制和情绪）和代谢概况。探索瘦和肥胖个体在体重减轻前后的代谢、心理行为和神经化学反应将提供允许以下的信息：1）使用正电子发射断层扫描（PET）成像评估响应于急性禁食和进食的中枢m-阿片系统; 2）鉴定与成功维持体重减轻相关的情绪和代谢测量之间的关系;（3）探讨代谢功能与心理行为表现的关系。 该应用程序的研究部分将允许候选人解决以下具体的培训目标：目标1：开发神经精神和行为评估的技能集，并在健康和患病人群中测量代谢参数。目的2：使用PET进行神经影像学研究。我们假设a）肥胖个体将呈现决策受损，B）减肥后肥胖个体的情绪和决策都将改善，c）肥胖个体的暴饮暴食与莫尔系统功能失调相关，以及d）减肥后肥胖个体的空腹莫尔BPND和来自标准餐的阿片样物质释放反应将增加。该项目具有很高的潜在意义，以帮助表征肥胖的代谢和心理行为反应，认为通过中央m-阿片系统共享一个共同的机制，并提供新的见解肥胖和维持体重减轻的神经激素和行为相关性。这种机制知识可能有助于为高危人群制定有针对性的干预措施以及肥胖症的潜在治疗策略。该项目将培养一名有前途的科学家，并帮助澄清肥胖症病理生理学的表型方面，这是一个重要的公共卫生优先事项。 拟议的K 01奖与NIH和NIDDK的使命非常一致，Burghardt博士的背景和职业目标符合NIH对转化科学的承诺。该项目将培养一名有前途的科学家，并帮助澄清肥胖病理生理学的表型方面，这是一个重要的公共卫生优先事项。

DESCRIPTION (provided by applicant): Obesity has reached epidemic levels in the United States. The rate of recidivism for long-term weight loss is substantial and presents a critical problem given the importance of obesity as a modifiable risk factor for diseases like type 2 diabetes. This K01 Mentored Research Scientist Award will support the candidate in establishing an independent research career using longitudinal psychobehavioral testing and neuroimaging to investigate the role of central opioid system response in obesity. The training component of this application builds on the candidate's exercise science and behavioral neuroscience background while providing a unique perspective to study the pathophysiology of obesity. The research component will examine psychobehavioral (impulse control and mood) and metabolic profiles of lean individuals and obese before and after weight loss. Probing the metabolic, psychobehavioral and neurochemical response in lean and obese individuals before and after weight loss will provide information allowing: 1) assessment of the central m-opioid systems in response to acute fasting and feeding using Positron Emission Tomography (PET) imaging; 2) identification of relationships between measures of mood and metabolism related to successful maintenance of weight loss; and 3) exploration of the relationship between metabolic function and psychobehavioral performance. The research component of this application will allow the candidate to address the following specific training aims: Aim 1: Develop skill-sets for neuropsychiatric and behavioral assessments and measurements of metabolic parameters in healthy and diseased populations. Aim 2: Conduct neuroimaging research using PET. We hypothesize that a) obese individuals will present impaired decision making, b) both mood and decision making will improve in obese individuals following weight-loss, c) overeating in obese individuals is associated with a dysregulation of MOR system function, and d) fasting MOR BPND and opioid release response from a standard meal will increase in obese individuals following weight loss. This project has high potential significance to help characterize the metabolic and psychobehavioral responses to obesity believed to share a common mechanism through central m-opioid systems, and provide novel insight into the neurohormonal and behavioral correlates of obesity and maintenance of weight loss. This mechanistic knowledge may help in the development of targeted interventions for high risk populations as well as potential treatment strategies for obesity. The project will train a promising scientist and help clarify phenotypic aspects of the pathophysiology of obesity, a significant public health priority. The proposed K01 award is well aligned with the missions of NIH and NIDDK, and Dr. Burghardt's background and career goals are in line with the commitment of NIH to translational science. The project will train a promising scientist and help clarify phenotypic aspects of the pathopyshiology of obesity, a significant public health priority.