TNF-α inhibits 3T3-L1 adipocyte differentiation without downregulating the expression of C/EBPβ and δ

Tumor necrosis factor-alpha (TNP-alpha) has been reported to inhibit adipocyte differentiation in which multiple transcription factors including CCAAT enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated receptor (PPAR) gamma play an important role. Induction of C/EBP alpha and PPAR gamma, which regulate the expression of many adipocyte-related genes, is dependent on the expression of C/EBP beta and C/EBP delta at the early phase of adipocyte differentiation. To elucidate the mechanism by which TNF-alpha inhibits adipocyte differentiation, we examined the effect of TNF-alpha on the expression of these transcription factors in mouse 3T3-L1 preadipocytes. TNF-alpha did not abrogate the induction of C/EBP beta and C/EBP delta in response to differentiation stimuli. In fully differentiated adipocytes, TNF-a rapidly induced C/EBP beta and C/EBP delta, whereas it downregulated the expression of C/EBP alpha and PPAR gamma. Our results suggest that TNF-alpha inhibits adipocyte differentiation independently of the downregulation of C/EBP beta and C/EBP delta.