Metabolic effects of the HIV protease inhibitor--saquinavir in differentiating human preadipocytes

Pharmacol Rep. 2013;65(4):937-50. doi: 10.1016/s1734-1140(13)71075-2.

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/EBPa, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adipocytes / cytology*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cells, Cultured
  • Endoplasmic Reticulum Stress / drug effects*
  • Endoplasmic Reticulum Stress / genetics
  • Gene Expression / drug effects
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxygen Consumption / drug effects*
  • Saquinavir / pharmacology*

Substances

  • HIV Protease Inhibitors
  • Adenosine Triphosphate
  • Saquinavir