Neurohormonal and Behavioral Correlates of Obesity and Weight Loss

描述(申请人提供)：肥胖症在美国已经达到流行水平。长期减肥的复发率很高，这是一个严重的问题，因为肥胖是2型糖尿病等疾病的一个可改变的风险因素。K01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。该应用程序的训练部分建立在候选人的运动科学和行为神经科学背景之上，同时为研究肥胖的病理生理学提供了独特的视角。研究部分将检查瘦人和肥胖者在减肥前后的心理行为(冲动控制和情绪)和代谢特征。探讨瘦人和肥胖者在减肥前后的代谢、心理行为和神经化学反应将提供以下信息：1)使用正电子发射断层扫描(PET)成像评估中枢m-阿片系统对急性禁食和进食的反应；2)确定与成功维持减肥相关的情绪和代谢指标之间的关系；3)探索代谢功能和心理行为表现之间的关系。这项申请的研究部分将使应聘者能够解决以下具体培训目标：目标1：在健康和患病人群中开发神经精神和行为评估和代谢参数测量的技能集。目的2：使用正电子发射计算机断层扫描进行神经影像研究。我们假设a)肥胖个体会出现决策能力受损，b)肥胖个体在减肥后情绪和决策会得到改善，c)肥胖个体暴饮暴食与MOR系统功能失调有关，d)肥胖个体在减肥后会增加空腹MOR BPND和标准膳食中阿片类药物的释放反应。该项目具有很高的潜在意义，有助于表征肥胖的代谢和心理行为反应，据信这些反应通过中枢m-阿片系统共享一个共同的机制，并为肥胖和维持减肥的神经激素和行为相关性提供新的见解。这种机械知识可能有助于为高危人群制定有针对性的干预措施，以及潜在的肥胖症治疗策略。该项目将培养一位有前途的科学家，并帮助澄清肥胖症的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。 建议的K01奖项与NIH和NIDDK的使命非常一致，Burghardt博士的背景和职业目标与NIH对翻译科学的承诺一致。该项目将培养一位有前途的科学家，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.