Transcriptional activation of SHP by PPAR-gamma in liver

Abstract

The mechanism of how PPAR gamma decrease gluconeogenic gene expressions in liver is still unclear. Since PPAR gamma is a transcriptional activator, it requires a mediator to decrease the transcription of gluconeogenic genes. Recently, SHP has been shown to mediate the bile acid-dependent down regulation of gluconeogenic gene expression in liver. This led us to explore the possibility that SHP may mediate the antigluconeogenic effect of PPAR gamma. In the present study, we have identified and characterized the presence of functional PPRE in human SHP promoter. We show the binding of PPAR gamma/RXR alpha heterodimer to the PPRE and increased SHP expression by rosiglitazone in primary rat hepatocytes. Taken together with the previous reports about the function of SHP on gluconeogenesis, our results indicate that SHP can mediate the acute antigluconeogenic effect of PPAR gamma. (C) 2007 Elsevier Inc. All rights reserved.