The overall goal of this proposal is to understand the role of inflammatory cytokines in the metabolic and skeletal abnormalities in HIV disease and to determine whether omega-3 fatty acid supplementation, in the form of fish oil, will alter the pathophysiology of these clinical disorders. Complementary and alternative medicines (CAM) are used widely among HIV-infected patients, often with the hope of preventing or treating complications associated with highly active antiretroviral therapy (HAART). Metabolic abnormalities, including peripheral fat wasting, central adiposity, insulin resistance, and dyslipidemia, and skeletal abnormalities (reduced bone mineral density and high bone turnover), are common in HIV-infected patients on HAART, yet their relationship is unclear. We hypothesize that these metabolic and skeletal abnormalities are related by abnormal inflammatory cytokine expression and that these conditions can be improved with fish oil, a widely-used CAM agent with anti-inflammatory properties. We have the following specific aims: 1) To understand the association between the metabolic and skeletal abnormalities in HIV-infected subjects and their relationship to inflammation, 2) To determine whether treatment with omega-3 fatty acids will have hypotriglyeridemic, anti-inflammatory, and anti-bone resorptive effects in a randomized trial of HIV-infected patients, and 3) To clarify the mechanisms of action of omega-3 fatty acids, namely the effect on lipolysis and bone turnover using stable isotope infusion techniques. To accomplish our specific aims, I intend to do a secondary analysis of data from two cohorts of HIV-infected subjects, and to then perform a randomized trial using a standardized fish oil product. These results will help to define the pathophysiology of the metabolic and skeletal abnormalities in HIV and evaluate the efficacy and potential mechanisms of action of an important complementary treatment. This proposal will also help me attain my goal of becoming an independent investigator in the area of CAM and HIV.
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