PPARγ in Adipogenesis and Insulin Resistance

Abstract

The differentiation of preadipocytes into adipocytes is regulated by a cascade of transcription factors that control the expression of a plethora of adipogenic genes [1,2]. Many studies during the last few years have identified PPARγ and members of the CCAAT/enhancer binding protein family, C/EBPs, as principal components of this transcriptional cascade. In particular, both PPARγ and C/EBPα appear to be positioned as central players in the process of preadipocyte differentiation since their expression occurs at approximately the same time and they function together to orchestrate the production of proteins controlling terminal differentiation. Two additional C/EBPs, C/EBPß and C/EBPδ are expressed very early during adipogenesis and appear to cooperate in inducing the expression of PPARγ and C/EBPα [3,4]. Other studies have implicated additional transcription factors in regulating various aspects of adipogenesis. Most notable is the sterol regulatory element binding protein, SREBPlc/ADDl, which has been shown to transactivate PPARγ gene expression and regulate the synthesis of PPARγ ligands [5,6]. In order to identify pathways that control the early phase of preadipocyte differentiation independent of C/EBPß and C/EBPδ, we cultured 3T3-L1 preadipocytes under conditions that selectively attenuate the activity of each of these C/EBPs. Furthermore, we were interested in defining transcriptional events that regulate the production of PPARγ ligands.