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Mol. Cell. Biol., Mar 1997, 1552-1561, Vol 17, No. 3
Copyright © 1997, American Society for Microbiology

Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription

EJ Schwarz, MJ Reginato, D Shao, SL Krakow and MA Lazar
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.


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