Transcriptional activation of SHP by PPAR-γ in liver

Abstract

The mechanism of how PPARγ decrease gluconeogenic gene expressions in liver is still unclear. Since PPARγ 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 PPARγ. In the present study, we have identified and characterized the presence of functional PPRE in human SHP promoter. We show the binding of PPARγ/RXRα 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 PPARγ.