Insulin and oleic acid increase PPARgamma2 expression in cultured mouse hepatocytes.
Hepatic PPARgamma expression is increased in several animal models of diabetes and obesity, and liver-specific overexpression of PPARgamma induces liver steatosis. The aim of this study was to investigate the regulation of PPARgamma expression in primary mouse hepatocytes. PPARgamma2, but not PPARgamma1, was up-regulated by insulin and to a lesser extent by oleic acid. Insulin increased transcription of the PPARgamma2 gene via phosphatidylinositol 3-kinase activation. The PPARgamma agonist, rosiglitazone, increased PPARgamma2 expression, but not PPARgamma1, 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, PPARgamma2 is increased in hepatocytes by oleic acid and insulin. These results may help to understand the regulation of PPARgamma expression in liver, which possibly plays a role in the development of liver steatosis.
Edvardsson
Ulrika
U
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden. ulrika.edvardsson@astrazeneca.com
Ljungberg
Anna
A
Oscarsson
Jan
J
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D019301:Oleic Acid / Q000008:administration & dosage*; D047495:PPAR gamma / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D015533:Transcriptional Activation / Q000187:drug effects
D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019301:Oleic Acid