Neural Mechanisms of Overeating Among Children Exposed to Gestational Diabetes Mellitus In Utero

项目总结 儿童肥胖率一直在急剧上升，这给医疗保健和福祉带来了巨大的代价。它是高度的 肥胖可能会持续到成年；因此，确定导致儿童肥胖的风险因素是极其重要的。 关键是及早采取预防策略，以降低肥胖率。研究表明，那些 在子宫中暴露于妊娠期糖尿病(GDM)的人患肥胖症的倾向增加。然而， 很少有人体研究旨在了解解释这种关系的机制。这项研究的目标是 检验以下假设：在子宫内接触GDM会导致调节饮食的大脑通路异常发育 这反过来又增加了儿童的食物摄入量和肥胖风险。为了实现这一目标，申请人和 她的团队计划1)检查GDM对食物摄入量的影响；2)GDM暴露与结构性和 大脑食欲和奖赏通路之间的功能联系；3)探索大脑回路的变化 参与进食行为会调节GDM暴露和食物摄入量增加之间的联系，从而增加 肥胖的风险。这将是人类首次使用多模式成像技术检查神经 妊娠期糖尿病暴露与肥胖风险之间的联系机制。 通过广泛的导师指导的培训、课程工作和讲习班、手稿和赠款写作、科学 在国家会议上发表演讲，候选人将实现三个培训目标1)加强关于GDM的知识 儿童生理学、儿童肥胖和营养(共同导师凯瑟琳·佩奇博士)；2)培养多种模式的技能 成像，并学习计算方法(例如，心理-生理-相互作用，独立分量 分析、DTI纤维跟踪、图论)，以在Dr. Paul Thompson(主要导师)和Neda Jahanshad(共同导师)；3)加强高级统计方面的技能 建模(例如，中介分析)(共同导师项安妮博士)。到拟议的培训期结束时， 候选人将在研究儿童肥胖风险的神经机制方面独树一帜 从不同学科的技能到孕妇宫内糖尿病，并竞争独立的R01应用程序。 此外，这个拟议的项目将帮助候选人朝着实现她的长期职业目标取得进展，这是 成为一名独立和创新的研究科学家，致力于研究肥胖的潜在机制 从神经科学、心理学和内分泌学的联合角度。

PROJECT SUMMARY Childhood obesity rate has been increasing dramatically, at great cost for health care and wellbeing. It is highly likely that obesity will persist into adulthood; thus, identifying risk factors contributing to childhood obesity is extremely critical so that prevention strategies can be taken early to reduce the obesity rate. Research suggests that children who were exposed to gestational diabetes mellitus (GDM) in utero have increased propensity of developing obesity. However, there are few human studies aimed to understand the mechanisms explaining this relationship. The goal of this study is to test the hypothesis that in utero exposure to GDM leads to abnormal development of brain pathways that regulate eating behavior, which in turn increases food intake and risk for obesity in children. To accomplish this goal, the applicant and her team plan to 1) examine effects of GDM on food intake; 2) associations of GDM exposure with structural and functional connections between brain appetite and reward pathways; 3) explore whether changes in brain circuitry involved in feeding behavior would mediate the link between GDM exposure and increased food intake thus increasing risk for obesity. This will be the first study in humans to use multi-modal imaging techniques to examine neural mechanisms of the link between GDM exposure and obesity risk. Through extensive mentor-directed training, course work and workshops, manuscript and grant writings, scientific presentations at national conferences, the candidate will achieve three training goals 1) strengthen knowledge about GDM physiology, pediatric obesity and nutrition in children (co-mentor Dr. Kathleen Page); 2) build skills in multi-modal imaging, and learn computational methods (e.g., psychological-physiological-interaction, independent component analysis, DTI fiber tracking, graph theory) to analyze functional and structural connectivity data under supervision of Drs. Paul Thompson (primary mentor) and Neda Jahanshad (co-mentor); 3) strengthen skills in advanced statistical modeling (e.g., mediation analysis) (co-mentor Dr. Anny Xiang). By the end of the proposed training period, the candidate will be positioned uniquely as a leader in investigating neural mechanisms for obesity risk in children exposed to maternal diabetes in utero with skills from various disciplines, and compete for an independent R01 application. Furthermore, this proposed project will help the candidate progress towards achieving her long-term career goal, which is to become an independent and innovative research scientist dedicated to investigating underlying mechanisms of obesity from a joint perspective of neuroscience, psychology and endocrinology.