PHARMACOLOGICAL BLOCKAGE OF A SELECTIVE CANNABINOID-1 RECEPTOR

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。 这项先导性研究旨在1)评估体重减轻可能导致的胰岛素敏感性变化，2)展示我们执行稳定同位素输注方案的能力，3)测量非酒精性脂肪性肝炎(NASH)患者脂蛋白中分泌并储存在肝脏中的脂肪(甘油三酯)的相对来源，并确定减肥药利莫那班(选择性大麻素1受体)对这一过程有何影响。将使用稳定同位素方法和肝脏活检来实现这些研究目标。过去对内源性大麻素拮抗剂(EA)治疗的研究表明，有益的代谢效应超出了单纯减肥的预期。在目前的研究中，将进行代谢研究，以检验这样的假设，即在低于影响食物摄入量的剂量下，使用EA利莫那班治疗将增加脂肪酸的使用并减少脂蛋白甘油三酯(TG)的产生。

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. This pilot study was designed to 1) evaluate the changes in insulin sensitivity that can occur with weight loss, 2) demonstrate our ability to perform stable isotope infusion protocols, and 3) measure the relative sources of fats (triglycerides) that are secreted in lipoproteins and stored in the liver in Nonalcoholic Steatohepatitis (NASH) and to determine what effects the weight loss drug Rimonabant (A selective cannabinoid-1 receptor) has on this process. Stable isotope methods and liver biopsy will be used to achieve these research objectives. Past studies of endocannabinoid antagonist (EA) treatment have shown beneficial metabolic effects beyond those expected from weight loss alone. In the present study, metabolic studies will be performed to test the hypotheses that treatment with the EA, Rimonabant, at a dose below that which would impact food intake, would increase fatty acid usage and reduce lipoprotein-triglyceride (TG) production.