NEUROENDOCRINE RESPONSE TO GASTRIC BYPASS IN NONHUMAN PRIMATES

该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。次级项目的主要支助 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 表示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。 肥胖是一种世界性的健康流行病。目前治疗肥胖症的方法之一是Roux-en-Y胃旁路术（RYGB），这已被证明是非常有效的。最近的研究出人意料地表明，RYGB主要通过改变能量平衡和体脂储存的生理控制来发挥作用。它影响多种生理系统，包括摄食行为、能量消耗和葡萄糖稳态的调节。此外，这种手术对糖尿病和其他代谢紊乱的有益影响似乎包括独立于体重减轻或食物摄入减少的机制。对于这些研究，我们正在研究RYGB在恒河猴中的生理作用，恒河猴是一种NHP，与许多人类一样，易受高脂肪饮食的体重增加和糖尿病促进作用的影响。本项目的目的是（1）建立肥胖恒河猴RYGB模型，并表征其对人类和啮齿动物中对RYGB高度反应的食物摄入、摄食行为、食物偏好和能量消耗的影响;（二）描述RYGB对葡萄糖稳态的影响，并确定这些影响的机制以及它们依赖于葡萄糖代谢的变化的程度。食物摄入或体重;（3）表征RYGB对调节摄食行为和能量平衡的下丘脑回路的作用;和（4）通过外周和门静脉血、选择的脑核、胰岛、肝和肌肉的基因表达和代谢谱来检查对RYGB的广泛代谢应答。

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. Obesity is a worldwide health epidemic. Among the current therapies for obesity is Roux-en-Y gastric bypass (RYGB), which has proven to be very effective. Recent studies have revealed, unexpectedly, that RYGB works primarily by altering the physiological control of energy balance and body fat storage. It affects a wide variety of physiological systems, including the regulation of ingestive behavior, energy expenditure and glucose homeostasis. Moreover, the beneficial effects of this operation on diabetes and other metabolic disorders appear to include mechanisms independent of weight loss or diminished food intake. For such studies, we are examining the physiological effects of RYGB in the Rhesus macaque, a species of NHP that, like many humans, is susceptible to the weight gain and diabetes-promoting effects of a high fat diet. The aims of the project are (1) to establish a model of RYGB in obese Rhesus macaques and to characterize its effects on food intake, ingestive behavior, food preference and energy expenditure, phenotypes that appear highly responsive to RYGB in humans and rodents; (2) to characterize the effects of RYGB on glucose homeostasis and determine the mechanisms of these effects and the degree to which they are dependent on changes in food intake or body weight; (3) to characterize the effect of RYGB on the hypothalamic circuitry regulating ingestive behavior and energy balance; and (4) to examine the broad metabolic response to RYGB through gene expression and metabolic profiling of peripheral and portal venous blood, selected brain nuclei, pancreatic islets, liver and muscle.