TNF-alpha inhibits 3T3-L1 adipocyte differentiation without downregulatingthe expression of C/EBP beta and delta

Tumor necrosis factor-alpha (TNP-alpha) has been reported to inhibit adipoc yte differentiation in which multiple transcription factors including CCAAT enhancer binding proteins (C/EBPs) and peroxisome proliferator-activated r eceptor (PPAR) gamma play an important role. Induction of C/EBP alpha and P PAR gamma, which regulate the expression of many adipocyte-related genes, i s dependent on the expression of C/EBP beta and C/EBP delta at the early ph ase of adipocyte differentiation. To elucidate the mechanism by which TNF-a lpha inhibits adipocyte differentiation, we examined the effect of TNF-alph a on the expression of these transcription factors in mouse 3T3-L1 preadipo cytes. TNF-alpha did not abrogate the induction of C/EBP beta and C/EBP del ta in response to differentiation stimuli. In fully differentiated adipocyt es, TNF-a rapidly induced C/EBP beta and C/EBP delta, whereas it downregula ted the expression of C/EBP alpha and PPAR gamma. Our results suggest that TNF-alpha inhibits adipocyte differentiation independently of the downregul ation of C/EBP beta and C/EBP delta.