Mallon Patrick W G
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Level 2, St Vincent's Medical Centre, St. Vincent's Hospital, Sydney, Darlinghurst, NSW 2010, Australia.
AIDS Rev. 2007 Jan-Mar;9(1):3-15.
HIV-associated lipodystrophy, arising as a result of long-term therapy with antiretroviral medications, is a complex syndrome characterized by changes in regional fat mass, dyslipidemia, and insulin sensitivity that, once established, is difficult to reverse. The syndrome arises largely as a result of effects of nucleoside reverse transcriptase inhibitors and protease inhibitors on lipid metabolism. Many of these effects have their basis at a molecular level with nucleoside reverse transcriptase inhibitors linked to inhibition of mitochondrial RNA transcription, depletion of mitochondrial DNA and mitochondrial dysfunction and protease inhibitors linked with adipocyte toxicity through interference with the function of essential cellular transcription factors such as sterol regulatory element binding protein 1c. These molecular toxicities can affect non-adipose tissues, and together with secondary effects on lipid and glucose metabolism of changes in body fat mass, help to contribute to the dyslipidemia and insulin resistance characteristic of this syndrome. This review will summarize what is known of the molecular mechanisms underlying HIV-associated lipodystrophy. A greater understanding of these mechanisms is essential if effective therapeutic options are to be found.
与人类免疫缺陷病毒（HIV）相关的脂肪代谢障碍是一种复杂的综合征，由长期使用抗逆转录病毒药物治疗引起，其特征是局部脂肪量改变、血脂异常和胰岛素敏感性异常，一旦形成就难以逆转。该综合征主要是由于核苷类逆转录酶抑制剂和蛋白酶抑制剂对脂质代谢的影响所致。这些影响大多基于分子水平，核苷类逆转录酶抑制剂与线粒体RNA转录抑制、线粒体DNA耗竭和线粒体功能障碍有关，而蛋白酶抑制剂则通过干扰关键细胞转录因子（如固醇调节元件结合蛋白1c）的功能与脂肪细胞毒性相关。这些分子毒性可影响非脂肪组织，并与体脂量变化对脂质和葡萄糖代谢的继发影响一起，促成该综合征的血脂异常和胰岛素抵抗特征。本综述将总结已知的与HIV相关脂肪代谢障碍的分子机制。若要找到有效的治疗方案，深入了解这些机制至关重要。
