PHARMACOLOGICAL BLOCKAGE OF A SELECTIVE CANNABINOID-1 RECEPTOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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. 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.