Effects of ritonavir on adipocyte gene expression: evidence for a stress-related response.

Obesity
Diane C Adler-WailesJack A Yanovski

Abstract

To understand the molecular mechanisms underlying the development of dyslipidemia and lipodystrophy that occurs after administration of aspartic acid protease inhibitors, we examined transcriptional profiles using cDNA microarrays in 3T3-L1 adipocytes exposed to 10 micromol/l ritonavir for 2-21 days. The expression levels of approximately 12,000 transcripts were assessed using the MgU74Av2 mouse microarray chip. Ritonavir altered gene expression of inflammatory cytokines, stress response genes localized to endoplasmic reticulum, oxidative stress genes, apoptosis-related genes, and expression of genes involved in cell adhesion and extracellular matrix remodeling. Microarray analysis also identified a novel gene downregulated by ritonavir, Cidea, whose expression levels may affect free-fatty acid metabolism. These changes suggest a unique, stress-related pattern in adipocytes induced by chronic exposure to the protease inhibitor, ritonavir.

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Citations

Nov 24, 2012·Nutrition Research Reviews·Cathríona Rosemary Loonam, Anne Mullen
Sep 17, 2009·Apoptosis : an International Journal on Programmed Cell Death·Carla J H van der KallenCasper G Schalkwijk
Oct 23, 2013·Pharmacological Reports : PR·Monika Bociąga-JasikAldona Dembińska-Kieć

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