Day Larry, Shikuma Cecilia, Gerschenson Mariana
Hawaii AIDS Clinical Research Program, University of Hawaii John A Burns School of Medicine, Honolulu, HI 96816, USA.
Ann N Y Acad Sci. 2004 Nov;1033:139-46. doi: 10.1196/annals.1320.013.
Lipodystrophy is an increasingly recognized complication of antiretroviral therapy for human immunodeficiency virus (HIV) infection. This syndrome encompasses both fat accumulation and wasting, which may be accompanied by metabolic derangements in glucose and lipid metabolism. While the precise mechanism of its development is not fully understood, lipodystrophy may represent chronic mitochondrial toxicity due to antiretroviral therapy and/or chronic HIV infection. Treatment of this condition has proven difficult, prompting research into agents that promote fat metabolism and mitochondrial function. L-carnitine is a nonessential micronutrient that regulates fatty acid transport into the mitochondrial matrix for metabolism via beta-oxidation. HIV-infected individuals on antiretroviral therapy may become deficient in this cofactor, limiting mitochondrial fat metabolism. While studies have shown some benefit for carnitine supplementation in cardiovascular disease, mitochondrial myopathies, and possibly male infertility, the data for its use in HIV-infected individuals are limited. Given its known physiologic function and the hypothesized mitochondrial basis for lipodystrophy, carnitine supplementation for this antiretroviral toxicity is reviewed. The available data from several small studies are inconclusive, although further research into this promising agent is warranted.
脂肪代谢障碍是一种越来越被认识到的人类免疫缺陷病毒(HIV)感染抗逆转录病毒治疗的并发症。该综合征包括脂肪堆积和消瘦,可能伴有葡萄糖和脂质代谢的紊乱。虽然其发生的确切机制尚未完全明确,但脂肪代谢障碍可能代表抗逆转录病毒治疗和/或慢性HIV感染所致的慢性线粒体毒性。这种疾病的治疗已被证明很困难,这促使人们研究促进脂肪代谢和线粒体功能的药物。左旋肉碱是一种非必需的微量营养素,它通过β氧化调节脂肪酸转运到线粒体基质中进行代谢。接受抗逆转录病毒治疗的HIV感染者可能会缺乏这种辅助因子,从而限制线粒体脂肪代谢。虽然研究表明补充肉碱对心血管疾病、线粒体肌病以及可能对男性不育症有一定益处,但其在HIV感染者中的应用数据有限。鉴于其已知的生理功能以及脂肪代谢障碍的线粒体假说基础,本文对补充肉碱治疗这种抗逆转录病毒毒性进行了综述。尽管有必要对这种有前景的药物进行进一步研究,但来自几项小型研究的现有数据尚无定论。