NEUROENDOCRINE RESPONSE TO GASTRIC BYPASS IN NONHUMAN PRIMATES

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。 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胃分流术(RYGB)，它已被证明非常有效。最近的研究出人意料地显示，RYGB主要通过改变能量平衡和体内脂肪储存的生理控制来发挥作用。它影响多种生理系统，包括调节摄食行为、能量消耗和葡萄糖动态平衡。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量减少的机制。在这类研究中，我们正在研究RYGB对恒河猴的生理影响。恒河猴是NHP的一个物种，像许多人类一样，容易受到高脂肪饮食的体重增加和促进糖尿病的影响。该项目的目的是(1)建立RYGB在肥胖恒河猴中的模型，并表征其对人类和啮齿动物对RYGB高度敏感的摄食、摄食行为、食物偏好和能量消耗的影响；(2)表征RYGB对血糖稳态的影响，并确定这些影响的机制和它们对食物摄入量或体重变化的依赖程度；(3)表征RYGB对调节消化行为和能量平衡的下丘脑回路的影响；以及(4)通过外周和门静脉血、选定的脑核、胰岛、肝脏和肌肉的基因表达和代谢谱来研究RYGB对RYGB的广泛代谢反应。

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.