Fish oil, inflammation, & metabolic complications in HIV

鱼油，炎症，

• 批准号: 7034534
• 负责人: TODD T BROWN
• 金额: $ 12.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7034534
• 关键词: AIDS therapy; HIV infections; acute phase protein; alternative medicine; bone density; clinical research; combination chemotherapy; diet therapy; drug adverse effect; human subject; human therapy evaluation; inflammation; insulin sensitivity /resistance; interleukin 6; marine animal oil; nutrition related tag; omega 3 fatty acid; patient oriented research; skeletal disorder; tumor necrosis factor alpha

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.

描述（由申请人提供）：本提案的总体目标是了解炎症细胞因子在HIV疾病的代谢和骨骼异常中的作用，并确定鱼油形式的omega-3脂肪酸补充剂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）在艾滋病毒感染者中广泛使用，通常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、中枢性肥胖、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治疗的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异常的炎性细胞因子表达有关，这些情况可以用鱼油改善，鱼油是一种广泛使用的具有抗炎特性的CAM剂。我们有以下具体目标：1）了解HIV感染受试者的代谢和骨骼异常之间的关联及其与炎症的关系，2）在HIV感染患者的随机试验中确定ω-3脂肪酸治疗是否具有降低甘油三酯、抗炎和抗骨吸收作用，和3）阐明ω-3脂肪酸的作用机制，即使用稳定同位素输注技术对脂解和骨转换的影响。为了实现我们的具体目标，我打算对两组HIV感染者的数据进行二次分析，然后使用标准化鱼油产品进行随机试验。这些结果将有助于定义HIV代谢和骨骼异常的病理生理学，并评估重要补充治疗的疗效和潜在作用机制。这个建议也将帮助我实现成为CAM和HIV领域独立调查员的目标。