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 肥胖很可能会持续到成年；因此，确定导致儿童肥胖的风险因素 肥胖是极其关键的，因此可以及早采取预防策略来降低肥胖率。 研究表明，在子宫内接触妊娠期糖尿病(GDM)的儿童有 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这样一个假设，即在子宫内暴露 妊娠期糖尿病导致调节饮食行为的大脑通路异常发育，进而 增加儿童的食物摄入量和肥胖风险。为了实现这一目标，申请者和她的团队计划 1)研究GDM对食物摄入量的影响；2)GDM暴露与结构和功能的关系 大脑食欲和奖赏通路之间的联系；3)探索大脑回路的变化 参与进食行为将调节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。这将是第一次在人体中使用多模式成像技术来 检查GDM暴露和肥胖风险之间联系的神经机制。 通过广泛的导师指导的培训、课程作业和研讨会、手稿和赠款 写作，在国家会议上发表科学演讲，候选人将实现三个培训目标1) 加强GDM生理学、儿童肥胖和儿童营养方面的知识(共同导师Dr。 凯瑟琳·佩奇)；2)培养多模式成像的技能，并学习计算方法(例如，心理学- 生理相互作用、独立成分分析、DTI纤维跟踪、图论)进行分析 在Paul Thompson博士(主要导师)和 Neda Jahanshad(共同导师)；3)加强高级统计建模(如中介分析)的技能 (共同导师项安妮博士)。在拟议的培训期结束时，候选人将被安排 在研究接触母婴的儿童肥胖风险的神经机制方面独树一帜 来自不同学科的技能，并竞争独立的R01应用程序。 此外，这个拟议的项目将帮助应聘者在实现其长期职业生涯方面取得进展 目标是成为一名独立而创新的研究科学家，致力于 从神经科学、心理学和内分泌学的联合角度探讨肥胖的潜在机制。

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.