Neuroendocrine Systems involved in Early-life Programming for Obesity and Diabetes

神经内分泌系统参与肥胖和糖尿病的早期规划

• 批准号: 10544493
• 负责人: Kathleen Alanna Page
• 金额: $ 67.76万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-13 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544493
• 关键词: Age; Animal Model; Appetite Regulation; Area; Biological; Body fat; Body mass index; Brain; Child; Child Support; Childhood diabetes; Complement; Computerized Medical Record; Coupled; Desire for food; Development; Diabetes Mellitus; Diagnosis; Documentation; Early Intervention; Early identification; Environment; Evolution; Exposure to; Future; Genetic; Gestational Diabetes; Glucose; Goals; Growth; Health; Hour; Human; Hyperglycemia; Hypothalamic structure; Impairment; Insulin Resistance; Intervention; Life; Link; Longitudinal Studies; Magnetic Resonance Imaging; Maternal Exposure; Maternal-Fetal Transmission; Metabolic Diseases; Mothers; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oral; Outcome; Participant; Pathway interactions; Personal Satisfaction; Pilot Projects; Play; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Prevalence; Prevention strategy; Risk; Role; Sampling; Satiation; Severities; Siblings; Signal Transduction; Structure; Testing; Translating; Weight Gain; Youth; aged; blood glucose regulation; brain pathway; cohort; critical period; diabetes risk; energy balance; fetal programming; high risk; in utero; innovation; insulin sensitivity; maternal diabetes; maternal obesity; maternal weight; metabolic phenotype; next generation; novel; obesity in children; obesity prevention; obesity risk; offspring; prenatal exposure; prepregnancy; prevent; response

! PROJECT SUMMARY/ABSTRACT The prevalence and severity of childhood obesity have increased dramatically and are coupled with alarming 30% rise in the prevalence of type 2 diabetes (T2D) in youth over the last decade. Mounting evidence suggests that exposures to maternal obesity and/or gestational diabetes mellitus (GDM) in utero contribute to these increases in childhood obesity and T2D. Studies from our group and others have shown that children who were exposed in utero to maternal obesity or GDM have greater adiposity and a higher risk for developing T2D compared to unexposed children. Studies in siblings discordant for maternal exposures suggest that the risk is in excess of that attributable to genetics and shared environment. The biological underpinnings of such maternal-fetal programming are poorly understood. Provocative studies in animal models reveal that intrauterine exposure to maternal obesity and/or diabetes results in alterations in the development of the hypothalamus, a brain area that is critical for the regulation of appetite and glucose homeostasis, leading to obesity and T2D later in life. To date, no studies have investigated the effects of exposure to maternal obesity or GDM on brain appetite pathways in humans. The overarching goal of this proposal is to test the hypothesis that in utero exposure to maternal obesity and/or GDM alters the structure and function of brain appetite pathways in ways that adversely impact energy balance and increases future risk for obesity and T2D in humans. Overall, these studies are highly innovative and have the potential to translate mechanistic findings in humans into early intervention strategies aimed at preventing the vicious cycle of maternal obesity/GDM and childhood obesity and T2D. !

呢 项目摘要/摘要 儿童肥胖的患病率和严重程度急剧增加，并与令人震惊 在过去十年中，年轻人中2型糖尿病（T2D）患病率上升了30％。越来越多的证据 表明子宫内对母性肥胖和/或妊娠糖尿病（GDM）的暴露有助于 这些增加了儿童肥胖和T2D。我们小组和其他人的研究表明孩子 在子宫内暴露于孕产妇肥胖或GDM的人具有更大的肥胖性，而发展的风险更高 与未暴露的儿童相比，T2D。兄弟姐妹的研究不一致的母亲暴露表明 风险超出了遗传学和共享环境的归因。这样的生物基础 孕产妇的编程知之甚少。动物模型中的挑衅性研究表明 宫内暴露于产妇肥胖和/或糖尿病会导致变化 下丘脑，这对于调节食欲和葡萄糖稳态至关重要的大脑区域，导致 肥胖和T2D以后。迄今为止，尚无研究调查孕产妇肥胖的影响 或人类大脑食欲途径的GDM。该提议的总体目标是检验假设 在子宫内暴露于产妇肥胖和/或GDM改变了大脑食欲的结构和功能 以不利影响能量平衡并增加肥胖和T2D的未来风险的方式 人类。总体而言，这些研究具有很高的创新性，并且有可能翻译机械发现 人类进入旨在防止孕产妇肥胖/GDM的恶性循环的早期干预策略和 儿童肥胖和T2D。 呢