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

子宫内妊娠糖尿病儿童暴饮暴食的神经机制

• 批准号: 10194480
• 负责人: Shan Luo
• 金额: $ 15.61万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194480
• 关键词: 10 year old; Adult; Age; Animal Model; Appetite Regulation; Area; Attention; Attenuated; Brain; Brain region; California; Calories; Child; Child Nutrition; Childhood; Collaborations; Computerized Medical Record; Computing Methodologies; Consumption; Corpus striatum structure; Coupling; Cues; Data; Desire for food; Development; Diagnosis; Diet; Dietary Assessment; Dietary intake; Diffusion Magnetic Resonance Imaging; Discipline; Eating; Eating Behavior; Educational workshop; Endocrinology; Energy Intake; Ethnic Origin; Exposure to; Face; Family; Feeding behaviors; Fetal Development; Fiber; Food; Food Intake Regulation; Functional Magnetic Resonance Imaging; Future; Genetic; Gestational Diabetes; Glucose; Goals; Grant; Health Care Costs; Human; Hyperphagia; Hypothalamic structure; Image; Imaging Techniques; Impairment; Joints; Knowledge; Learning; Life; Link; Manuscripts; Measurement; Measures; Medial; Mediating; Mediation; Mentors; Metabolic; Methods; Motivation; Multimodal Imaging; National Institute of Diabetes and Digestive and Kidney Diseases; Neurosciences; Neurosecretory Systems; Obesity; Parents; Pathogenesis; Pathway interactions; Personal Satisfaction; Physiological; Physiology; Population; Positioning Attribute; Pregnancy; Prevention strategy; Psychology; Public Health; Reporting; Research; Rest; Rewards; Risk; Risk Factors; Role; Sampling; Scientist; Seeds; Siblings; Signal Transduction; Statistical Methods; Statistical Models; Structure; Supervision; Testing; Training; Work; Writing; base; blood glucose regulation; brain circuitry; brain pathway; career; cohort; density; food environment; frontal lobe; functional MRI scan; glucose tolerance; graph theory; imaging modality; in utero; independent component analysis; innovation; maternal diabetes; member; metabolic phenotype; modifiable lifestyle factors; multimodality; neuroimaging; neuromechanism; obesity development; obesity in children; obesity risk; offspring; prenatal exposure; prepregnancy obesity; psychologic; response; reward circuitry; sex; skills; symposium; white matter

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.

项目摘要 儿童肥胖率一直在急剧上升，为医疗保健和福祉付出了巨大代价。极有 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非常重要的。 这一点至关重要，以便及早采取预防策略，降低肥胖率。研究表明， 在子宫内暴露于妊娠期糖尿病（GDM）的孕妇有增加的肥胖倾向。然而，在这方面， 很少有人类研究旨在了解解释这种关系的机制。本研究的目的是 测试子宫内暴露于GDM导致调节进食的大脑通路异常发育的假设 行为，这反过来又会增加儿童的食物摄入量和肥胖风险。为了实现这一目标，申请人和 她团队计划1）检查GDM对食物摄入的影响; 2）GDM暴露与结构和 大脑食欲和奖励途径之间的功能联系; 3）探索大脑回路的变化是否 参与喂养行为的人会介导GDM暴露和食物摄入增加之间的联系， 肥胖的风险。这将是第一项使用多模态成像技术来检查人类神经系统的研究。 GDM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、手稿和赠款著作， 在国家会议上的演讲，候选人将实现三个培训目标1）加强对GDM的知识 生理学，儿童肥胖症和儿童营养（共同导师Kathleen Page博士）; 2）建立多模式技能 成像，并学习计算方法（例如，心理-生理-相互作用，独立成分 分析，DTI纤维跟踪，图论），以分析功能和结构连接数据的监督下，博士。 Paul Thompson（主要导师）和Neda Jahanshad（共同导师）; 3）加强高级统计技能 建模（例如，调解分析）（共同导师向安妮博士）。在拟议培训期结束时， 候选人将被定位为独特的领导者，在调查神经机制的儿童肥胖风险暴露 在子宫内的母亲糖尿病与来自不同学科的技能，并竞争一个独立的R 01应用程序。 此外，这个拟议的项目将有助于候选人朝着实现她的长期职业目标，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视角。