MATERNAL HIGH FAT DIET AND THE MELANOCORTIN SYSTEM IN THE OFFSPRING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在过去的几十年里，儿童肥胖症的数量急剧增加。这一建议的一般假设是，孕期和新生儿早期的饮食和代谢健康对儿童代谢性疾病的发展有重大贡献。在这些研究中，我们开发了一个非人类灵长类(NHP)模型，即高脂肪/高热量饮食导致的母体肥胖/糖尿病，这使我们能够确定对子代体重动态平衡的即时和长期影响。这一建议的具体焦点是下丘脑中的黑素皮质素神经元，它们对于食物摄入量和能量平衡的稳态反馈控制至关重要，以响应外周肥胖信号。我们预测，在怀孕和哺乳期间摄入高脂肪/卡路里的食物会导致这些神经元在胎儿期的异常发育，导致长期的重新编程。有了这些发育异常，我们预计后代更容易早发肥胖症并最终患上糖尿病。最后，我们将确定在怀孕期间给肥胖/糖尿病NHP喂食健康饮食是否对后代代谢异常的发展具有保护作用。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患代谢性疾病；这是一种与美国大多数怀孕相匹配的母体表型。这些信息将对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.