MATERNAL HIGH FAT DIET AND THE MELANOCORTIN SYSTEM IN THE OFFSPRING

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在过去的几十年里，儿童肥胖症急剧增加。这项建议的一般假设是，怀孕期间和新生儿早期的饮食和代谢健康对儿童代谢疾病的发展有重大影响。对于这些研究，我们开发了一种高脂肪/热量饮食诱导的母体肥胖/糖尿病的非人灵长类动物（NHP）模型，使我们能够确定对后代体重稳态的直接和长期影响。该建议的具体焦点是下丘脑中的黑皮质素神经元，其对于响应于外周肥胖信号的食物摄入和能量平衡的稳态反馈控制至关重要。我们预测，在怀孕期间和哺乳期间食用高脂肪/卡路里饮食将导致这些神经元在胎儿期的异常发育，导致长期重编程。由于这些发育异常，我们预计后代易患早发性肥胖症，最终患糖尿病。最后，我们将确定是否喂养一个健康的饮食肥胖/糖尿病NHP特别是在怀孕期间是保护对后代的代谢异常的发展。通过这些研究，我们希望证明，仅仅是超重和吃高脂肪饮食就会导致婴儿代谢疾病;这是一种与美国大多数孕妇相匹配的母体表型。这些信息对于设计可行的预防措施至关重要，并具有巨大的公共卫生影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Over the past several decades there has been a dramatic increase in childhood obesity. The general hypothesis of this proposal is that diet and metabolic health during pregnancy and the early neonatal period significantly contribute to the development of metabolic diseases in children. For these studies we developed a nonhuman primate (NHP) model of high fat/calorie diet-induced maternal obesity/diabetes that is allowing us to determine the immediate and long-term effects on body weight homeostasis in offspring. The specific focus of this proposal is the melanocortin neurons in the hypothalamus, which are critical for the homoeostatic feedback control of food intake and energy balance in response to peripheral adiposity signals. We predicted that consumption of a high fat/calorie diet during pregnancy and during nursing will cause an abnormal development of these neurons during in the fetal period, leading to a long-term reprogramming. With these developmental abnormalities, we expect the offspring to be predisposed to early onset obesity and ultimately diabetes. Finally, we will determine if feeding a healthy diet to obese/diabetic NHPs specifically during pregnancy is protective against the development of metabolic abnormalities in the offspring. With these studies, we hope to demonstrate that simply being overweight and eating a high fat diet causes metabolic disease in babies; a maternal phenotype that matches the majority of pregnancies in the United States. This information will be critical for designing a viable prevention and has enormous public health implications.