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

描述（由申请人提供）：怀孕期间患有糖尿病的母亲的孩子有很高的肥胖风险。其中一些风险可能是遗传的。然而，涉及兄弟姐妹在子宫内接触糖尿病不一致的研究，以及比较糖尿病母亲和父亲的后代的单独研究表明，子宫内环境有额外的影响。动物模型中具有争议性的研究表明，暴露于母体糖尿病改变的宫内环境所驱动的代谢印记导致调节能量稳态的脑通路重组。这些变化促进了食物摄入和肥胖。调节食欲和食物摄入的大脑通路的类似改变可能导致人类肥胖。然而，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。

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.