PPAR gamma ligand-dependent induction of STAT1, STAT5A, and STAT5B during adipogenesis

We have recently demonstrated that STAT1, STAT5A, and STAT5B are induced du ring adipogenesis of cultured preadipocytes in a differentiation-dependent manner. Members of the C/EBP and PPAR families of transcription factors hav e also been shown to be induced during adipocyte differentiation and to pla y a significant role in the regulation of fat-specific genes, In this inves tigation, we have examined the ability of C/EBPs and PPARs to contribute to STAT protein expression during conversion of non-precursor fibroblasts to functionally mature adipocytes, For this study, NIH-3T3 fibroblasts enginee red to ectopically co-express C/EBP beta and C/EBP delta under the control of a tetracycline-responsive, inducible expression system were utilized to assess STAT expression during controlled adipogenesis. Data presented here demonstrate that STAT1, STAT5A, and STAT5B, but not STAT3 and STAT6, were i nduced in a tetracycline-responsive manner during the differentiation of th ese engineered fibroblasts, The STAT protein accumulation resulting from C/ EBP expression was tightly coupled to the morphological conversion of fibro blasts to adipocytes and represents an expression profile identical to that reported for mature adipocytes in vivo. Data are also presented demonstrat ing that STAT protein accumulation and adipocyte conversion occurred only d uring controlled conditions leading to the expression of PPAR gamma and tha t the expression of these three STATs was tightly regulated in a PPAR gamma ligand dose-response fashion. These data illustrate that the cascade of tr anscriptional events leading to adipogenesis regulate the STAT family of tr anscription factors and that the differentiation dependent upregulation of STAT protein expression is regulated downstream of PPAR gamma in a Ligand-d ependent manner. (C) 1999 Academic Press.