HIV protease inhibitors block adipocyte differentiation independently of lamin A/C
HIV protease inhibitors block adipocyte differentiation independently of lamin A/C
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DOI：
10.1097/01.aids.0000186827.91408.90
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发表时间：
2005-10-14
期刊：
影响因子：
3.8
通讯作者：
Kennedy, BK
中科院分区：
文献类型：
--
作者：
Kudlow, BA;Jameson, SA;Kennedy, BK
Objectives: To determine the importance of lamin A/C for fat cell differentiation in vitro and for the anti-adipogenic activity of HIV protease inhibitors such as indinavir.Methods: Lipodystrophy-associated and processing-defective mutants of lamin A were stably expressed at high levels in 3T3-L1 pre-adipocytes. Additionally, 3T3-L1 pre-adipocytes with stable reduction of lamin A/C or emerin were derived. The cells were differentiated for 8 days into mature adipocytes in the presence or absence of indinavir or nelfinavir.Results: 3T3-L1 cells stably expressing high levels of lipodystrophy-associated or processing-defective mutants of lamin A differentiated with comparable efficiencies to control cells. Similarly, cells with dramatically reduced lamin A levels differentiated as efficiently as controls. Although indinavir stimulated the accumulation of unprocessed lamin A, cells with dramatically reduced lamin A/C levels and no detectable prelamin A remained responsive to an indinavir-induced inhibition of adipogenesis.Conclusions: The ability of HIV protease inhibitor to stimulate the accumulation of unprocessed lamin A is neither necessary nor sufficient to explain their anti-adipogenic activity. Furthermore, lamin A/C plays a minimal role in the differentiation of 3T3-L1. (c) 2005 Lippincott Williams & Wilkins.
