HIV 蛋白酶抑制剂与肥胖。
HIV protease inhibitors and obesity.
机构信息
Department of Medicine, University of California, Davis, Sacramento, CA 95817, USA.
出版信息
Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):478-85. doi: 10.1097/MED.0b013e32833dde87.
PURPOSE OF REVIEW
To review the current scientific literature and recent clinical trials on HIV protease inhibitors and their potential role in the pathogenesis of lipodystrophy and metabolic disorders.
RECENT FINDINGS
HIV protease inhibitor treatment may affect the normal stimulatory effect of insulin on glucose and fat storage. Further, chronic inflammation from HIV infection and protease inhibitor treatment trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. This process leads to a pathologic cycle of lipodystrophy and lipotoxicity, a proatherogenic lipid profile, and a clinical phenotype of increased central body fat distribution similar to the metabolic syndrome.
SUMMARY
Protease inhibitors are a key component of antiretroviral therapy and have dramatically improved the life expectancy of HIV-infected individuals. However, they are also associated with abnormalities in glucose/lipid metabolism and body fat distribution. Further studies are needed to better define the pathogenesis of protease inhibitor-associated metabolic and body fat changes and their potential treatment.
目的综述
回顾 HIV 蛋白酶抑制剂的现有科学文献和最近的临床试验，以及它们在脂肪营养不良和代谢紊乱发病机制中的潜在作用。
最近的发现
HIV 蛋白酶抑制剂治疗可能会影响胰岛素对葡萄糖和脂肪储存的正常刺激作用。此外，HIV 感染和蛋白酶抑制剂治疗引起的慢性炎症会引发细胞内稳态应激反应，对中间代谢产生不良影响。生理结果是总脂肪细胞储存能力降低，而剩余的脂肪细胞抵抗进一步的脂肪储存。这个过程导致脂肪营养不良和脂毒性的病理循环、动脉粥样硬化脂质谱以及类似于代谢综合征的中央体脂分布增加的临床表型。
总结
蛋白酶抑制剂是抗逆转录病毒治疗的一个关键组成部分，极大地提高了 HIV 感染者的预期寿命。然而，它们也与葡萄糖/脂质代谢和体脂分布异常有关。需要进一步的研究来更好地定义蛋白酶抑制剂相关代谢和体脂变化的发病机制及其潜在的治疗方法。
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