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

子宫内患糖尿病的儿童肥胖风险的神经机制

基本信息

批准号：
8853280
负责人：
Kathleen Alanna Page
金额：
$ 8.25万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8853280
关键词：
Age Animal Model Appetite Regulation Attenuated Body mass index Brain Brain region Child Corpus striatum structure Cues Data Desire for food Development Diabetes Mellitus Diabetic mother Eating Environment Ethnic Origin Exposure to Fathers Feeding behaviors Food Functional Magnetic Resonance Imaging Gender Genetic Gestational Diabetes Glucose Goals Health Hispanics Homeostasis Human Hypothalamic structure Imaging Techniques Ingestion Intervention Life Magnetic Resonance Imaging Metabolic Mothers Obesity Outcome Perinatal Exposure Pregnancy Recording of previous events Regulation Research Rewards Risk Siblings Spin Labels Techniques Testing base blood oxygen level dependent brain pathway cohort feeding fetal programming high risk imprint in utero innovation intergenerational maternal diabetes neuromechanism obesity risk offspring response therapy design

项目摘要

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.

描述（由申请人提供）：怀孕期间患有糖尿病的母亲的孩子患肥胖症的风险很高。其中一些风险可能是遗传的。但是，涉及兄弟姐妹在子宫内暴露于糖尿病的研究和比较糖尿病母亲后代与父亲的单独研究表明宫内环境的额外作用。动物模型中的挑衅性研究表明，由于暴露于孕产妇糖尿病的宫内环境而驱动的代谢烙印会导致调节能量稳态的大脑途径的重组。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途径的类似变化可能有助于人类肥胖的发展。然而，尚无研究研究宫内暴露于糖尿病对人类脑喂养电路的影响。该应用的总体目标是检验以下假设：在子宫内暴露于Gestationa糖尿病（GDM）中会导致涉及人类喂养行为的脑途径的改变。这些研究结合了fMRI技术的组合来比较暴露于子宫内妊娠糖尿病的儿童与未暴露于妊娠糖尿病的儿童之间的食欲和能量稳态涉及的大脑途径。通过我们正在进行的有关宫内妊娠糖尿病对肥胖风险的影响的研究，我们有一个既定的，有或没有GDM病史的母亲的西班牙裔儿童。我们的初步数据支持其他人的发现，这些发现表明在暴露于子宫内妊娠糖尿病的后代中肥胖过多。该应用的目的是了解发生这些代际效应的潜在神经机制。