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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 在过去的几十年里，儿童肥胖症急剧增加。该提案的总体假设是，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显着影响。在这些研究中，我们开发了高脂肪/热量饮食引起的母亲肥胖/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。该提案的具体重点是下丘脑中的黑皮质素神经元，它对于响应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，怀孕期间和哺乳期间摄入高脂肪/热量饮食将导致胎儿期这些神经元发育异常，从而导致长期重新编程。由于这些发育异常，我们预计后代容易患上早发性肥胖症，并最终患上糖尿病。最后，我们将确定在怀孕期间为肥胖/糖尿病 NHP 提供健康饮食是否可以防止后代出现代谢异常。通过这些研究，我们希望证明，仅仅是超重和高脂肪饮食就会导致婴儿代谢疾病；与美国大多数怀孕情况相匹配的母亲表型。这些信息对于设计可行的预防措施至关重要，并且具有巨大的公共卫生影响。