Neural mechanisms for obestity risk in children exposed to diabetes in utero

描述（由申请人提供）：母亲在怀孕期间患有糖尿病的儿童患肥胖症的风险很高。其中一些风险可能是遗传性的。然而，涉及子宫内暴露于糖尿病的兄弟姐妹不一致的研究和比较糖尿病母亲与父亲的后代的单独研究表明宫内环境的额外影响。在动物模型中的挑衅性研究表明，暴露于母体糖尿病改变的宫内环境驱动的代谢印记导致调节能量稳态的脑通路的重组。这些变化促进食物摄入和肥胖。调节食欲和食物摄入的大脑通路的类似改变可能有助于人类肥胖的发展。然而，没有研究调查宫内暴露于糖尿病对人类大脑供血回路的影响。 本申请的总体目标是检验子宫内暴露于妊娠糖尿病（GDM）导致参与人类摄食行为调节的脑通路改变的假设。这些研究使用功能磁共振成像技术的组合，比较在子宫内暴露于和未暴露于妊娠糖尿病的儿童之间参与食欲和能量稳态调节的脑通路。通过我们正在进行的关于宫内暴露于妊娠期糖尿病对肥胖风险的影响的研究，我们建立了一个有或没有GDM记录史的母亲的西班牙裔儿童队列。我们的初步数据支持了其他人的发现，即在子宫内暴露于妊娠期糖尿病的后代过度肥胖。这个应用程序的目标是了解这些代际效应发生的潜在神经机制。

DESCRIPTION (provided by applicant): Children of mothers who had diabetes during pregnancy are at high risk for developing obesity. Some of this risk is likely to be genetic. However, studies involving siblings discordant for exposure to diabetes in utero and separate studies comparing offspring of diabetic mothers versus fathers indicate an additional effect of the intrauterine environment. Provocative studies in animal models suggest that metabolic imprinting driven by exposure to the altered intrauterine environment of maternal diabetes leads to a reorganization of brain pathways that regulate energy homeostasis. These changes promote food intake and obesity. Similar alterations in brain pathways that regulate appetite and food intake could contribute to the development of obesity in humans. However, no studies have investigated the effects of intrauterine exposure to diabetes on brain feeding circuitry in humans. The overall goal of this application is to test the hypothesis that in utero exposure to gestationa diabetes mellitus (GDM) results in alterations in brain pathways involved in the regulation of feeding behavior in humans. These studies use a combination of fMRI techniques to compare brain pathways involved in the regulation of appetite and energy homeostasis between children exposed and children not exposed to gestational diabetes in utero. Through our ongoing studies on the effects of intrauterine exposure to gestational diabetes on risk for obesity, we have an established cohort of Hispanic children of mothers with and without a documented history of GDM. Our preliminary data support findings of others demonstrating excess obesity in the offspring exposed to gestational diabetes in utero. The goal of this application is to understand potential neural mechanisms by which these intergenerational effects occur.