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

描述(申请人提供)：怀孕期间患有糖尿病的母亲的孩子患肥胖症的风险很高。其中一些风险很可能是遗传的。然而，涉及在子宫中接触糖尿病的兄弟姐妹的研究，以及比较糖尿病母亲和父亲的子女的单独研究表明，宫内环境的另一种影响。在动物模型中的挑衅性研究表明，暴露于母亲糖尿病宫内环境的改变导致代谢印记导致调节能量稳态的大脑路径的重组。这些变化促进了食物的摄入和肥胖。调节食欲和食物摄入量的大脑通路的类似变化可能会导致人类肥胖的发展。然而，还没有研究调查宫内暴露于糖尿病对人类大脑喂养回路的影响。 这项应用的总体目标是检验这样一种假设，即在子宫内暴露于妊娠期糖尿病(GDM)会导致参与人类进食行为调节的大脑通路发生变化。这些研究使用功能磁共振技术的组合来比较子宫内暴露于妊娠期糖尿病和未暴露于妊娠期糖尿病的儿童中参与调节食欲和能量动态平衡的大脑通路。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，我们已经建立了母亲有和没有妊娠期糖尿病病史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中出现了过度肥胖。这项应用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.