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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

基本信息

批准号：
10434598
负责人：
Shan Luo
金额：
$ 7.81万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
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/10434598
关键词：
10 year old Administrative Supplement Adult Age Animal Model Appetite Regulation Area Attenuated Award Brain COVID-19 pandemic California Calories Child Child Nutrition Collaborations Computerized Medical Record Computing Methodologies Consumption Corpus striatum structure Coupling Cues Data Data Analyses Data Collection Desire for food Development Diagnosis 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 Financial Support Food Food Intake Regulation Genetic Gestational Diabetes Glucose Goals Grant Health Care Costs Human Hyperphagia Hypothalamic structure Image Imaging Techniques Impairment Joints Knowledge Learning Link Manuscripts Measurement Measures Medial Mediating Mediation Mentors Metabolic Motivation Multimodal Imaging Neurosciences Obesity Parents Pathway interactions Personal Satisfaction Physiological Physiology Positioning Attribute Pregnancy Prevention strategy Psychology Public Health Reporting Research Rewards Risk Risk Factors Scientist Seeds Siblings Signal Transduction Statistical Methods Statistical Models Structure Supervision Testing Time Training Work Writing base blood glucose regulation brain circuitry brain pathway career career development cohort density food environment frontal lobe functional MRI scan glucose tolerance graph theory in utero independent component analysis innovation maternal diabetes member metabolic phenotype neuromechanism obesity development obesity in children obesity risk offspring prenatal exposure prepregnancy obesity psychologic research and development response reward circuitry sex skills symposium white matter

项目摘要

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。它肥胖很可能会持续到成年;因此，确定导致儿童肥胖的危险因素，肥胖症极为严重，因此可以及早采取预防策略，以降低肥胖率。研究表明，在子宫内暴露于妊娠期糖尿病（GDM）的儿童，增加发展肥胖的倾向。然而，很少有人类研究旨在了解解释这种关系的机制。这项研究的目的是检验子宫内暴露的假设， GDM导致大脑调节饮食行为的通路异常发育，增加儿童的食物摄入量和肥胖风险。为了实现这一目标，申请人及其团队计划 1）检查GDM对食物摄入的影响; 2）GDM暴露与结构和功能的关联大脑食欲和奖励途径之间的联系; 3）探索大脑回路的变化是否参与进食行为的基因会介导GDM暴露和食物摄入增加之间的联系，增加肥胖的风险。这将是第一项使用多模态成像技术对人类进行的研究，研究GDM暴露与肥胖风险之间联系的神经机制。通过广泛的导师指导培训、课程和讲习班、手稿和赠款写作，在国家会议上的科学演讲，候选人将实现三个培训目标1）加强对GDM生理学、儿童肥胖和儿童营养的认识（共同导师Dr。 Kathleen Page）; 2）建立多模态成像技能，并学习计算方法（例如，心理上- 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）的监督下获得功能和结构连接性数据， Neda Jahanshad（共同导师）; 3）加强高级统计建模技能（例如，调解分析）（共同导师项安妮博士）。在拟议的培训期结束时，候选人将被定位作为研究暴露于母亲的儿童肥胖风险的神经机制的领导者，糖尿病在子宫内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生涯的进展目标，这是成为一个独立的和创新的研究科学家，致力于调查从神经科学、心理学和内分泌学的联合角度探讨肥胖的潜在机制。