HIGH FAT DIET INDUCED ALTERATIONS IN GENE EXPRESSION IN THE NONHUMAN PRIMATE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 描述（由申请人提供）：肥胖是一种全球性的健康流行病，是冠心病、高血压、脂肪肝和2型糖尿病发生率增加的主要原因。在过去的30年中，超重和肥胖的流行率在美国的成人和儿童中都有所增加。大约6000万成年人，或30%的成年人口，现在肥胖。众所周知，许多因素导致肥胖和相关疾病的发展。临床研究和啮齿动物模型研究都为肥胖和相关疾病的发病机制及其对大脑的影响提供了关键见解。然而，人类和啮齿动物研究受到限制，可能会阻碍其直接转化为有效的治疗干预措施。非人灵长类动物（NHP）已成为整合啮齿动物和人类研究数据的关键模型。这项建议的总体目标是在高脂饮食诱导的肥胖（DIO）的NHP模型中进行平行的生理学、基因组学和蛋白质组学分析。该模型的主要优势在于：1）DiO在NHP中的进展与在人类中的进展相似，并且该模型发展了相关疾病的全谱; 2）动物的实验环境被仔细控制，使得食物摄入被准确地知道;以及3）动物的代谢表型的广泛表征是可行的。 公共相关性（由申请人提供）：本提案的具体目的是表征NHP中与肥胖相关的下丘脑基因和蛋白质表达水平的变化。虽然这些研究主要是描述性的和相关的，但这些信息将为一般科学界提供一个关键的数据库，并将使临床和基础科学家能够产生关于大脑内系统的新的特定假设，这些系统与肥胖有关。这些数据也将为未来开发治疗代谢性疾病的疗法提供关键见解

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Obesity is a worldwide health epidennic and a major contributor to the increased occurrence of coronary heart disease, hypertension, fatty liver disease, and type 2 diabetes. During the past 30 years, the prevalence of overweight and obesity has increased for both adults and children in the United States. About 60 million adults, or 30% of the adult population, are now obese. It is well accepted that many factors contribute to the development of obesity and associated disorders. Both clinical research and studies in rodent models have provided key insights into the pathogenesis of obesity and associated diseases, as well as their impact on the brain. However, human and rodent studies are subject to limitations that can hamper their direct translation to effective therapeutic interventions. The nonhuman primate (NHP) has emerged as a critical model for integrating data from rodent and human studies. The overall objective of this proposal is to perform parallel physiological, genomic, and proteomic analyses in a NHP model of high-fat diet-induced obesity (DIO). The major strengths of this model are that: 1) The progression of DiO in the NHP is similar to that in humans, and this model develops the full spectrum of associated diseases; 2) the experimental environment of the animals is carefully controlled so that food intake is accurately known; and 3) Extensive characterization of the metabolic phenotype of the animals is feasible. PUBLIC RELEVANCE (provided by applicant): The specific objectives of this proposal are to characterize changes in gene and protein expression levels in the hypothalamus that are associated with obesity in the NHP. While these studies are primarily descriptive and correlative, this information will provide a critical database for the general scientific community and will allow both clinical and basic scientists to generate novel specific hypothesis about systems within the brain that become dysfunctional in association with obesity. These data will also provide key insights for the future development of therapeutics for the treatment of metabolic diseases