Fish oil, inflammation, & metabolic complications in HIV

描述(申请人提供)：本提案的总体目标是了解炎性细胞因子在HIV疾病代谢和骨骼异常中的作用，并确定以鱼油形式补充omega-3脂肪酸是否会改变这些临床疾病的病理生理学。补充和替代药物(CAM)在艾滋病毒感染患者中被广泛使用，通常是希望预防或治疗与高效抗逆转录病毒疗法(HAART)相关的并发症。代谢异常，包括外周脂肪消耗、中心性肥胖、胰岛素抵抗和血脂异常，以及骨骼异常(骨密度降低和骨转换高)，在接受HAART的HIV感染患者中很常见，但它们之间的关系尚不清楚。我们假设这些代谢和骨骼异常与炎症细胞因子的异常表达有关，鱼油可以改善这些情况，鱼油是一种广泛使用的具有抗炎特性的CAM试剂。我们有以下具体目标：1)了解HIV感染者代谢和骨骼异常之间的联系及其与炎症的关系；2)在一项针对HIV感染患者的随机试验中，确定omega-3脂肪酸治疗是否具有降血糖、抗炎和抗骨吸收作用，以及3)利用稳定的同位素输注技术，阐明omega-3脂肪酸的作用机制，即对脂解和骨转换的影响。为了实现我们的特定目标，我打算对两组艾滋病毒感染者的数据进行二次分析，然后使用一种标准化的鱼油产品进行随机试验。这些结果将有助于确定HIV代谢和骨骼异常的病理生理学，并评估一种重要的补充治疗的疗效和潜在的作用机制。这项提议还将帮助我实现成为CAM和艾滋病毒领域的独立调查员的目标。

DESCRIPTION (provided by applicant): 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.