Brain reward as a link between insulin resistance and weight status in Hispanic c

描述（由申请人提供）：本提案的总体目标是研究不同程度的胰岛素抵抗对肥胖和正常体重的西班牙裔儿童大脑奖励回路的影响。脑奖励回路活动将使用功能磁共振成像（fMRI）测定两组西班牙裔儿童（8 - 11岁）的胰岛素抵抗程度。这一提议是验证一个统一假设的第一步，即外周胰岛素抵抗不仅是肥胖的后果，而且反过来通过破坏中央食物摄入调节来促进正能量平衡。此外，该研究计划旨在为我提供重要的培训，为独立和跨学科的研究生涯做好准备。Adam博士近期的职业目标是：1)成为使用fMRI的专家，并分析收集到的数据，以帮助阐明食物摄入调节的核心机制；2)向儿童人群扩展食物摄入调节、肥胖和2型糖尿病机制的知识；3)能够胜任脑解剖学和与奖励处理有关的不同解剖结构的研究；4)加深对胰岛素敏感性与肥胖之间机制关系的认识；5)指导本科生和研究生，为他们从事儿童肥胖和2型糖尿病的防治工作做好准备。总体的长期职业目标是成为一名独立的跨学科研究者，专注于了解儿童肥胖的食物摄入调节。与此KO1相关的具体培训活动将包括：1)michael Goran博士、Richard Bergman博士、Dianne Lattemann博士、Zhong-Lin Lu博士和Weigensberg博士的直接指导；2)参加研讨会和正式课程，在完成研究和职业发展所需的学科领域和方法技能方面接受培训（如神经科学、功能磁共振成像方法、生物统计学、拨款写作）；3)参加会议以提高科学专业知识，建立专业网络，并提供展示和讨论研究结果的机会。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to examine the effect of different degrees of insulin resistance on brain reward circuits in obese and normal-weight Hispanic children. Brain reward circuit activity will be determined using functional magnetic resonance imaging (fMRI) in two groups of Hispanic children (aged 8 - 11 years) who provide a large range of insulin resistance. This proposal is a first step in testing the unifying hypothesis that peripheral insulin resistance is not only a consequence of obesity but in turn contributes to positive energy balance through a disruption of central food intake regulation. Furthermore, the research proposal is designed to provide important training to prepare me for an independent and inter-disciplinary research career. Dr. Adam's immediate career goals are to: 1) become an expert in the use of fMRI as well as analyze the collected data to help elucidate the central mechanisms of food intake regulation; 2) expand knowledge on mechanisms of food intake regulation, obesity and type 2 diabetes to the pediatric population; 3) become competent in research regarding brain anatomy and the different anatomical structures that are involved in reward processing; 4) deepen knowledge about the mechanistic relationship between insulin sensitivity and obesity; and, 5) mentor undergraduate and graduate students in preparing them for careers in prevention and treatment of childhood obesity and type 2 diabetes. The overall long-term career goal is to become an independent and inter-disciplinary investigator focused on the understanding of food intake regulation in childhood obesity. The specific training activities associated with this KO1 will involve: 1) direct mentorship from Dr.Michael Goran, Dr. Richard Bergman, Dr. Dianne Lattemann, Dr. Zhong-Lin Lu and Dr. Weigensberg; 2) attending seminars and formal classes to be trained in the subject areas and methodological skills necessary to complete the study as well as in career development (eg neuroscience; fMRI methodology; biostatistics; grant writing); and 3) attend conferences to improve scientific expertise, create a professional network and provide exposure to present and discuss study findings. PUBLIC HEALTH RELEVANCE: The proposed study will examine how insulin resistance may not only be a consequence of obesity but also a cause for overeating through a disruption of central food intake regulation. The results will substantiate the importance of insulin sensitivity as a primary target for obesity treatment and early age intervention for successful prevention of obesity.