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PPAR Research
Volume 2010 (2010), Article ID 325183, 16 pages
http://dx.doi.org/10.1155/2010/325183
Review Article

Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

1UMR INSERM U991, Faculté des Sciences Pharmaceutiques et Biologiques, 35043 Rennes, France
2Université de Rennes 1, 35065 Rennes, France
3Biologie Servier, 45520 Gidy, France
4Institut de Recherches Servier, 92150 Suresnes, France
5Institut de Recherches Servier, 92400 Courbevoie, France

Received 8 June 2010; Accepted 15 July 2010

Academic Editor: Barbara Abbott

Copyright © 2010 Alexandra Rogue et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor (PPAR ) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPAR is expressed at a much lower level in liver than in adipose tissue, PPAR agonists exert various PPAR -dependent effects in liver in addition to PPAR -independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals.