Neurohormonal and Behavioral Correlates of Obesity and Weight Loss

肥胖和减肥的神经激素和行为相关性

• 批准号: 9039273
• 负责人: Paul R Burghardt
• 金额: $ 9.29万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-10 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9039273
• 关键词: Neurohormonal; Behavioral; Correlates; Obesity; Weight

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.

描述（由申请人提供）：肥胖已达到美国的流行水平。长期体重减轻的累犯率是实质性的，并且鉴于肥胖症是2型糖尿病等疾病的可修改风险因素的重要性，这是一个关键的问题。这项K01指导研究科学家奖将支持候选人建立独立的研究职业，该研究使用纵向心理行为测试和神经影像学研究中央阿片类药物系统反应在肥胖症中的作用。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的基础上，同时提供了研究肥胖病理生理学的独特观点。 该研究成分将检查精神病（冲动控制和情绪）以及体重减轻前后的瘦人和肥胖的代谢特征。在体重减轻之前和之后，探测瘦和肥胖个体中的代谢，心理和神经化学反应将提供信息允许：1）评估中枢M-阿片类系统，以响应急性禁食和使用正电子发射断层扫描（PET）成像来评估急性禁食和进食； 2）鉴定与成功维持体重减轻有关的情绪度量与新陈代谢之间的关系； 3）探索代谢功能与精神行为表现之间的关系。 该应用程序的研究部分将使候选人能够解决以下特定培训目的：目标1：为健康和患病人群中代谢参数的神经精神和行为评估以及测量的技能集。目标2：使用PET进行神经影像研究。我们假设a）a）肥胖个体会提出决策受损，b）心情和决策会在减肥后的肥胖个体中有所改善，c）肥胖个体中暴饮暴食与MOR系统功能的失调以及d）禁食有关体重减轻后肥胖个体的MOR BPND和阿片类药物释放反应将增加。该项目具有很高的潜在意义，可以帮助表征对肥胖症的代谢和心理反应，该反应被认为是通过中枢M-阿片类药物共享共同机制的，并提供了对肥胖和体重减轻的神经性和行为相关性的新见解。这种机械知识可能有助于开发针对高风险人群的有针对性干预措施以及肥胖的潜在治疗策略。该项目将培训一位有前途的科学家，并帮助阐明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。 拟议的K01奖与NIH和NIDDK的任务非常一致，Burghardt博士的背景和职业目标与NIH对转化科学的承诺一致。该项目将培训一位有前途的科学家，并帮助澄清肥胖病理学的表型方面，这是一个重要的公共卫生优先事项。