Kosmiski Lisa A, Miller Heidi L, Klemm Dwight J
Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA.
Antivir Ther. 2006;11(2):187-95.
The use of nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infection is clearly linked to the development of subcutaneous fat atrophy. Until recently, however, in vitro studies of adipocytes have shown no or only modest and inconsistent effects of these agents on adipocyte biology. This is in contrast to the protease inhibitors (PIs), which are also linked to the development of HIV lipodystrophy. These agents have relatively consistent inhibitory effects on the differentiation of cultured adipocytes, and have occasionally been found to have other effects on adipocyte biology as well. We aimed to explore more thoroughly the effects of NRTIs and combinations of antiretroviral agents commonly used in clinical practice on multiple aspects of adipocyte biology using the 3T3-L1 adipocyte cell line. We found that when used individually, NRTIs decrease cell survival but only lamivudine significantly alters lipid accumulation. However, NRTI and dual NRTI-PI combinations do significantly decrease lipid accumulation in 3T3-L1 adipocytes, have a much greater detrimental impact on cell survival and decrease adipocyte differentiation.
使用核苷类逆转录酶抑制剂（NRTIs）治疗HIV感染显然与皮下脂肪萎缩的发生有关。然而，直到最近，对脂肪细胞的体外研究表明，这些药物对脂肪细胞生物学没有影响，或者只有适度且不一致的影响。这与蛋白酶抑制剂（PIs）形成对比，蛋白酶抑制剂也与HIV脂肪代谢障碍的发生有关。这些药物对培养的脂肪细胞分化具有相对一致的抑制作用，并且偶尔也被发现对脂肪细胞生物学有其他影响。我们旨在使用3T3-L1脂肪细胞系更全面地探索NRTIs以及临床实践中常用的抗逆转录病毒药物组合对脂肪细胞生物学多个方面的影响。我们发现，单独使用时，NRTIs会降低细胞存活率，但只有拉米夫定能显著改变脂质积累。然而，NRTI与NRTI-PI双联组合确实会显著降低3T3-L1脂肪细胞中的脂质积累，对细胞存活有更大的有害影响，并降低脂肪细胞分化。
