LONG-TERM EFFECTS OF PYY 3-36 ON RHESUS MACAQUE ENERGY HOMEOSTASIS

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。子项目及 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。 肥胖是发达国家面临的主要健康挑战之一，显著增加了冠心病和糖尿病的风险。最近的研究表明，一个人的身体质量指数（BMI）每超过25个“点”，心脏病的风险就会相应增加（男性5%，女性7%）。除了可怕的人力成本之外，还有与如此肥胖人口的医疗保健相关的重大经济成本。据估计，美国医疗保健支出的9.4%与“肥胖和不活动”直接相关，而最近因糖尿病造成的费用估计为每年980亿美元。近年来，在鉴定对调节能量稳态重要的基因和途径方面取得了巨大进展，特别是瘦素-受体对（Lepob）和瘦素受体（Lepr，LR）。白色脂肪细胞产生瘦素，瘦素或功能性瘦素受体的缺乏导致病态肥胖。不幸的是，瘦素对大多数人类肥胖症并不是有效的治疗方法。肽YY（PYY）在进餐后由肠道分泌，与摄入的卡路里成比例，并且组成性地裂解为PYY 3 -36。我们最近已经证明，PYY 3 -36在施用给啮齿动物和人类时抑制食物摄入。我们还证明，每天腹膜内注射PYY 3 -36可持续抑制大鼠的食物摄入和显著的体重减轻。在我们开始测试PYY 3 -36长期治疗对人类肥胖症的影响之前，确定在非人灵长类动物中是否观察到类似的效果是至关重要的。通过与Judy卡梅隆博士和Frank Koegler博士的合作，我们非常适合测试PYY 3-36对恒河猴肥胖症的中期治疗效果。如果这些实验显示出预期的食物摄入量和身体脂肪的减少，这将加速PYY 3-36作为治疗人类肥胖症的治疗剂的开发。

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. Obesity is one of the major health challenges facing the developed world, significantly increasing the risk of coronary disease, and of diabetes. It has recently been shown that for every "point" by which a person's body mass index (BMI) exceeds 25, there is an associated increase (5% in men and 7% in women) in the risk of cardiac disease. Beyond the terrible human costs there are significant economic costs associated with health care for such an obese population. An estimated 9.4% of US healthcare expenditure is directly related to "obesity and inactivity," while recent costs due to diabetes were estimated at $98 billion per annum. In recent years tremendous advances have been made identifying genes and pathways important for regulating energy homeostasis, in particular the hormone-receptor pair leptin (Lepob) and leptin receptor (Lepr, LR). White adipose cells produce leptin and absence of leptin or functional leptin receptors causes morbid obesity. Unfortunately, leptin has not been an effective treatment for most human obesity. Peptide YY (PYY) is secreted by the gut following a meal in proportion to ingested calories, and is constitutively cleaved to PYY3-36. We have recently demonstrated that PYY3-36 inhibits food intake when administered to rodents and humans. We have also demonstrated that daily intraperitoneal injections of PYY3-36 causes sustained inhibition of food intake and significant weight loss in rats. It is crucial to determine if a similar effect is seen in nonhuman primates before we begin testing the effects of long-term PYY3-36 treatment on human adiposity. In collaboration with Dr. Judy Cameron and Dr. Frank Koegler, we are ideally positioned to test the effects of medium-term treatment with PYY 3-36 on rhesus macaque adiposity. If these experiments show the expected decrease in food intake and body fat, it will accelerate the development of PYY 3-36 as a therapeutic agent for the treatment of human obesity.