Transcriptional activation of PIK3R1 by PPARγ in adipocytes

Phosphatidylinositol 3-kinase (PI3K) plays an important role in the metabolic actions of insulin and is required for adipogenesis. Regulatory subunit 1 of PI3K (PIK3R1) is a critical component of the PI3K signaling pathway. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a key regulator of adipogenesis. Although the PPAR gamma agonist rosiglitazone induces the expression of PIK3R1, the transcriptional regulation of PIK3R1 in adipocytes remains unknown. In this study, we investigated whether PIK3R1 is a direct target of PPAR gamma. The level of PIK3R1 expression in 3T3-L1 cells was increased after the induction of adipocyte differentiation and was also induced by overexpression of PPAR gamma. Furthermore, the upregulation of PPAR gamma-mediated PIK3R1 expression enhanced the insulin-stimulated AKT activation in 3T3-L1 cells. Two putative peroxisome proliferator response elements (PPREs) in the PIK3R1 promoter were identified as PPAR gamma binding sites. By chromatin immunoprecipitation, we observed that PPAR gamma interacts with the two PPRE regions of the PIK3R1 promoter in mature adipocytes. In addition, luciferase reporter assays showed that the -1183/-1161 and -573/-551 regions of the PIK3R1 promoter contain essential elements for PPAR gamma binding. Taken together, these results suggest that PPAR gamma is essential for the transcriptional activity of PIK3R1 during adipogenesis.