Metabolic effects of the HIV protease inhibitor – saquinavir in differentiating human preadipocytes
2013
Abstract Background The iatrogenic, HIV-related lipodystrophy is associated with development of the significant metabolic and cardiovascular complications. The underlying mechanisms of antiretroviral (ARV) drugs are not completely explored. Methods The aim of the study was to characterize effects of the protease inhibitor (PI) – saquinavir (SQV) on metabolic functions, and gene expression during differentiation in cells (Chub-S7) culture. Results SQV in concentrations observed during antiretroviral therapy (ART) significantly decreased mitochondrial membrane potential (MMP), oxygen consumption and ATP generation. The effects were greater in already differentiated cells. This was accompanied by characteristic changes in the expression of the genes involved in endoplasmic reticulum (ER) stress, and differentiation (lipid droplet formation) process such as: WNT10a, C/EBPα, AFT4, CIDEC, ADIPOQ, LPIN1. Conclusions The results indicate that SQV affects not only metabolic (mitochondrial) activity of adipocytes, but affects the expression of genes related to differentiation and to a lesser extent to cell apoptosis.
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