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，付出了医疗保健和福祉的巨大成本。它肥胖很可能会持续到成年。因此，确定导致儿童的危险因素肥胖至关重要，因此可以尽早采取预防策略来降低肥胖率。研究表明，子宫内接触妊娠糖尿病（GDM）的儿童已经增加肥胖的倾向。但是，人类研究的目的很少解释这种关系的机制。这项研究的目的是检验子宫暴露中的假设到GDM导致调节饮食行为的大脑途径的异常发展，这反过来又增加食物摄入量和儿童肥胖风险。为了实现这一目标，申请人和她的团队计划至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与奖励途径之间的联系； 3）探索大脑电路的变化是否参与进食行为将介导GDM暴露与食物摄入量增加之间的联系增加肥胖的风险。这将是人类使用多模式成像技术的第一项研究检查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的培训，课程工作和讲习班，手稿和授予著作，国家会议的科学演讲，候选人将实现三个培训目标1）加强有关儿童的GDM生理学，小儿肥胖和营养的知识（Co-centor Dr. 凯瑟琳·佩奇（Kathleen Page））; 2）在多模式成像中建立技能，并学习计算方法（例如，心理学 - 生理相互作用，独立组件分析，DTI光纤跟踪，图理论）用于分析 DR的监督下的功能和结构连接数据。保罗·汤普森（主要导师）和 NEDA Jahanshad（联合学）； 3）加强高级统计建模的技能（例如，调解分析）（联合官员Anny Xiang博士）。到拟议的培训期结束时，候选人将被定位作为调查神经机制的神经机制的独特领导者子宫内的糖尿病具有来自各个学科的技能，并竞争独立的R01应用程序。此外，这个提议的项目将有助于候选人进步，以实现她的长期职业目标，即成为一名独立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共同角度来看，肥胖的潜在机制。