Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1. Implications for adipocyte differentiation and metabolism

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor implicated in adipocyte differentiation and insulin sensitivity. W e investigated whether PPAR gamma expression is dependent on the activity o f adipocyte differentiation and determination factor 1/sterol regulatory el ement binding protein 1 (ADD-1/SREBP1), another transcription factor associ ated with both adipocyte differentiation and cholesterol homeostasis. Ectop ic expression of ADD-1/SREBP-1 in 3T3-L1 and HepG2 cells induced endogenous PPAR gamma mRNA levels. The related transcription factor SREBP-2 likewise induced PPAR gamma expression. In addition, cholesterol depletion, a condit ion known to result in proteolytic activation of transcription factors of t he SREBP family, induced PPAR gamma expression and improved PPRE-driven tra nscription. The effect of the SREBPs on PPAR gamma expression was mediated through the PPAR gamma 1 and -3 promoters. Both promoters contain a consens us E-box motif that mediates the regulation of the PPAR gamma gene by ADD-1 /SREBP-1 and SREBP-2. These results suggest that PPAR gamma expression can be controlled by the SREBP family of transcription factors and demonstrate new interactions between transcription factors that can regulate different pathways of lipid metabolism.