Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines
Por:
Diaz-Delfin, J, Gutierrez, MD, Gallego-Escuredo, JM, Domingo, JC, Mateo, MG, Villarroya, F, Domingo, P, Giralt, M
Publicada:
1 ago 2011
Resumen:
The non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz are drugs of choice for initial antiretroviral treatment for HIV-1 infection. Although NNRTIs have not traditionally been associated with the appearance of adipose alterations, recent data suggest that efavirenz may contribute to adipose tissue alterations in antiretroviral-treated patients, consistent with its ability to impair differentiation of adipocytes in cell cultures. No such effects have been reported for nevirapine, the other most commonly used NNRTI. In this study, we determined the effects of nevirapine on differentiation, gene expression and release of regulatory proteins (adipokines and cytokines) in differentiating human adipocytes, and compared them with those of efavirenz. Efavirenz caused a dose-dependent repression of adipocyte differentiation that was associated with down-regulation of the master adipogenesis regulator genes SREBP-1, PPAR gamma and C/EBP alpha, and their target genes encoding lipoprotein lipase, leptin and adiponectin, which are key proteins in adipocyte function. In contrast, nevirapine does not affect adipogenesis and causes a modest but significant coordinate increase in the expression of SREBP-1, PPAR gamma and C/EBP alpha and their target genes only at a concentration of 20 mu M. Whereas efavirenz caused a significant increase in the release of pro-inflammatory cytokines (interleukin [IL]-8, IL-6, monocyte chemoattractant protein-1), plasminogen activator inhibitor type-1 and hepatocyte growth factor (HGF), nevirapine either had no effect on these factors or decreased their release (IL-6 and HGF). Nevirapine significantly increased adiponectin release, whereas efavirenz strongly repressed it. Moreover, nevirapine inhibited preadipocyte endogenous reverse transcriptase activity, whereas efavirenz did not alter it. It is concluded that, in contrast with the profound anti-adipogenic and pro-inflammatory response elicited by efavirenz, nevirapine does not impair adipogenesis. (C) 2011 Elsevier B.V. All rights reserved.
Filiaciones:
Diaz-Delfin, J:
Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain
Gutierrez, MD:
Autonomous Univ Barcelona, Infect Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Red Invest SIDA RIS, Barcelona, Spain
Gallego-Escuredo, JM:
Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain
Domingo, JC:
Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain
Mateo, MG:
Autonomous Univ Barcelona, Infect Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Red Invest SIDA RIS, Barcelona, Spain
Villarroya, F:
Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain
Domingo, P:
Autonomous Univ Barcelona, Infect Dis Unit, Hosp Santa Creu & St Pau, Barcelona, Spain
Red Invest SIDA RIS, Barcelona, Spain
Giralt, M:
Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain
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