PHARMACOLOGICAL BLOCKAGE OF A SELECTIVE CANNABINOID-1 RECEPTOR

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。 这项初步研究的目的是：1）评估体重减轻时胰岛素敏感性的变化，2）证明我们执行稳定同位素输注方案的能力，和3）测量脂肪的相对来源（甘油三酯），分泌的脂蛋白和储存在肝脏中的非酒精性脂肪性肝炎（NASH），并确定什么影响减肥药物利莫那班（一种选择性大麻素-1受体）对这一过程有影响。稳定同位素方法和肝活检将用于实现这些研究目标。 过去的内源性大麻素拮抗剂（EA）治疗的研究表明，有益的代谢作用超出了预期的体重减轻。在本研究中，将进行代谢研究以检验以下假设：以低于影响食物摄入的剂量使用EA、利莫那班治疗将增加脂肪酸使用并减少脂蛋白-甘油三酯（TG）产生。

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. 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.