EFFICACY OF A MELANOCORTIN AGONIST ON ENERGY BALANCE AND GLYCEMIC CONTROL IN OB

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。 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”，心脏病的风险就会增加。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，而最近由于糖尿病造成的费用估计为每年980亿美元。制药公司对开发一种治疗性干预措施产生了浓厚的兴趣，这种干预措施将抑制食物摄入并导致受控和安全的体重减轻。大脑中的黑皮质素神经元产生一种神经肽，其有效地抑制食物摄入，刺激能量消耗并调节外周葡萄糖稳态。黑皮质素系统在啮齿动物中对人类的重要性显而易见，黑皮质素基因的突变或基因缺失会导致早发性病态肥胖。事实上，黑皮质素系统的突变是人类肥胖最常见的单基因原因。本研究的总体目的是确定用黑皮质素激动剂治疗是否可以改善饮食诱导肥胖的恒河猴模型中的身体肥胖和葡萄糖稳态。本研究的具体目标是：1）确定用于抑制食物摄入的黑皮质素激动剂的有效剂量，2）确定使用黑皮质素激动剂的长期治疗是否可以减少食物摄入、身体肥胖和改善胰岛素敏感性。

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 in the risk of cardiac disease. 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. There has become intense interest by pharmaceutical companies to develop a therapeutic intervention that will inhibit food intake and cause controlled and safe weight loss. The melanocortin neurons in the brain produce a neuropeptide that potently inhibits food intake, stimulates energy expenditure and regulates peripheral glucose homeostasis. The importance of the melanocortin system is clearly evident in rodents to humans, whereby mutations or genetic deletion of melanocortin genes cause early onset morbid obesity. In fact mutations of the melanocortin system are the most common monogenic cause of obesity in humans. The overall aim of this study is to determine if treatment with a melanocortin agonist can improve body adiposity and glucose homeostasis in a rhesus macaque model of diet induced obesity. The specific goals of this study are to 1) identify an effective dose of melanocortin agonist for the inhibition of food intake, and 2) determine if long-term treatment with a melanocortin agonist can reduce food intake, body adiposity, and improve insulin sensitivity.