C/EBPalpha reverses the anti-adipogenic effects of the HIV protease inhibitor nelfinavir.
Nelfinavir and other HIV protease inhibitors effectively suppress morbidity and mortality in HIV-infected patients. However, therapeutic use of HIV protease inhibitors has been temporally associated with the development of a lipodystrophy/insulin resistance syndrome and some evidence suggests that HIV protease inhibitors may be the causative agent. We report here that nelfinavir promotes loss of cytoplasmic triglyceride from fully differentiated adipocytes and inhibits preadipocyte differentiation at biologically relevant concentrations. Forced expression of the adipogenic transcription factor C/EBPalpha rescues some of the anti-adipogenic effects of nelfinavir. These results suggest that nelfinavir may mediate an anti-adipogenic effect by antagonizing expression of C/EBPalpha.
Dowell
Paul
P
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA. dowellp@jhmi.edu <dowellp@jhmi.edu>
Lane
M Daniel
MD
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017320:HIV Protease Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D019888:Nelfinavir / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; D017320:HIV Protease Inhibitors; D014280:Triglycerides; D019888:Nelfinavir