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

好了！ 项目摘要/摘要 儿童肥胖症的患病率和严重程度急剧增加，并伴随着令人担忧的 在过去的十年中，年轻人中2型糖尿病(T2D)的患病率上升了30%。越来越多的证据 表明在子宫内暴露于母亲肥胖和/或妊娠期糖尿病(GDM)有助于 儿童肥胖症和T2D的增加。我们小组和其他人的研究表明，儿童 在子宫内暴露于母体肥胖或妊娠期糖尿病的人有更多的肥胖和更高的发展风险 T2D与未暴露的儿童进行比较。对与母亲接触不一致的兄弟姐妹的研究表明， 风险超过了可归因于遗传和共享环境的风险。这种现象的生物学基础 人们对母婴编程知之甚少。在动物模型中的挑衅性研究表明 宫内暴露于母亲肥胖和/或糖尿病会导致母体发育的改变 下丘脑是调节食欲和葡萄糖动态平衡的关键大脑区域，导致 肥胖和T2D在生活的后期。到目前为止，还没有研究调查母亲肥胖的影响。 或妊娠期糖尿病对人类大脑食欲通路的影响。这项提议的首要目标是检验这一假设 在子宫内暴露于母亲肥胖和/或妊娠期糖尿病会改变大脑食欲的结构和功能 途径会对能量平衡造成不利影响，并增加未来肥胖和T2D的风险 人类。总体而言，这些研究具有很高的创新性，并有可能将机械性的发现转化为 将人类纳入旨在防止产妇肥胖/妊娠期糖尿病恶性循环的早期干预战略和 儿童肥胖与T2D的关系。 好了！

! 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. !