Hepatic PPAR gamma expression is increased in several animal models of diabetes and obesity, and liver-specific overexpression of PPAR gamma induces liver steatosis. The aim of this study was to investigate the regulation of PPAR gamma expression in primary mouse hepatocytes. PPAR gamma 2, but not PPAR gamma 1, was up-regulated by insulin and to a lesser extent by oleic acid. Insulin increased transcription of the PPAR gamma 2 gene via phosphatidylinositol 3-kinase activation. The PPAR gamma agonist, rosiglitazone, increased PPAR gamma 2 expression, but not PPAR gamma 1, only in the presence of insulin. Also aP2 mRNA expression was induced by rosiglitazone to a higher degree in the presence of insulin, while acyl-CoA oxidase was increased independently of insulin. In summary, PPAR gamma 2 is increased in hepatocytes by oleic acid and insulin. These results may help to understand the regulation of PPAR gamma expression in liver, which possibly plays a role in the development of liver steatosis. (c) 2005 Elsevier Inc. All rights reserved.