MATERNAL HIGH FAT DIET AND THE MELANOCORTIN SYSTEM IN THE OFFSPRING

母亲的高脂肪饮食和后代的黑皮质素系统

• 批准号: 8357879
• 负责人: KEVIN L GROVE
• 金额: $ 4.36万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357879
• 关键词: Body Weight; Child; Consumption; Development; Diabetes Mellitus; Diet; Discipline of Nursing; Eating; Fatty acid glycerol esters; Feedback; Food Energy; Funding; Grant; Health; Homeostasis; Hypothalamic structure; Long-Term Effects; Metabolic; Metabolic Diseases; Modeling; National Center for Research Resources; Neonatal; Neurons; Obesity; Overweight; Peripheral; Phenotype; Pregnancy; Prevention; Primates; Principal Investigator; Public Health; Research; Research Infrastructure; Resources; Signal Transduction; Source; System; United States; United States National Institutes of Health; cost; design; diabetic; early onset; energy balance; feeding; fetal; good diet; neuron development; nonhuman primate; obesity in children; offspring; response

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在过去的几十年中，儿童肥胖症急剧增加。该提议的总体假设是，怀孕期间和新生儿早期的饮食和代谢健康显着有助于儿童代谢疾病的发展。在这些研究中，我们开发了一种非人类灵长类动物（NHP）模型的高脂肪/卡路里饮食诱导的孕产妇肥胖/糖尿病，这使我们能够确定对后代体重稳态的直接和长期影响。该提案的特定重点是下丘脑中的黑素皮质素神经元，这对于响应外周肥胖信号的均经反馈控制食物摄入和能量平衡至关重要。我们预测，在怀孕期间和护理期间消耗高脂肪/卡路里饮食将在胎儿期间导致这些神经元异常发育，从而导致长期重编程。有了这些发育异常，我们预计后代会倾向于早期发作肥胖和最终糖尿病。最后，我们将确定在怀孕期间特别保护肥胖/糖尿病NHP的健康饮食是否对后代代谢异常的发展进行保护。通过这些研究，我们希望证明，超重和吃高脂肪饮食会导致婴儿的代谢疾病。与美国大多数怀孕相匹配的母体表型。这些信息对于设计可行的预防并具有巨大的公共卫生影响至关重要。