Signaling pathways utilized by tumor necrosis factor receptor 1 in adipocytes to suppress differentiation

Tumor necrosis factor-alpha (TNF alpha) has profound effects on cultured ad ipocytes, one of which is the inhibition of terminal differentiation. Previ ous studies in TNF receptor (TNFR)deficient preadipocytes have demonstrated that the anti-adipogenic effect of both secreted and transmembrane TNF(x i s mediated solely by TNFR1. In this study, we performed a structure-functio n analysis of the intracellular domains of TNFR1 and investigated the signa ling pathway(s) involved in TNFR1-mediated inhibition of adipocyte differen tiation. Our results show that repression of adipogenesis required the juxt amembrane and death domains and was independent of the pathways involving n uclear factor KB and neutral sphingomyelinase. (C) 2001 Published by Elsevi er Science BAI. on behalf of the Federation of European Biochemical Societi es.