RETINOIC ACID BLOCKS ADIPOGENESIS BY INHIBITING C EBP-BETA-MEDIATED TRANSCRIPTION/

Adipocyte differentiation is thought to involve sequential induction o f the transcription factors C/EBP beta, peroxisome proliferator-activa ted receptor gamma (PPAR gamma), and C/EBP alpha. C/EBP alpha expressi on is both necessary and sufficient for adipocyte differentiation. Her e we report that ectopic expression of either C/EBP alpha or C/EBP bet a induces PPAR gamma expression and adipogenesis and that retinoic aci d (RA) completely inhibits adipogenesis by either form of C/EBP. In st udies of normal preadipocytes, RA does not prevent C/EBP beta inductio n but blocks induction of PPAR gamma, C/EBP alpha, and adipogenesis. I n transient transfection studies, liganded RA receptor (RAR) specifica lly blocks transcriptional activation by either C/EBP alpha or C/EBP b eta. These results strongly suggest that C/EBP alpha substitutes for C /EBP beta to induce adipocyte differentiation and that liganded RAR in hibits adipogenesis by blocking C/EBP beta-mediated induction of downs tream genes.