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.
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