Tumor necrosis factor-α (TNFα) has profound effects on cultured adipocytes, one of which is the inhibition of terminal differentiation. Previous studies in TNF receptor (TNFR)-deficient preadipocytes have demonstrated that the anti-adipogenic effect of both secreted and transmembrane TNFα is mediated solely by TNFR1. In this study, we performed a structure–function analysis of the intracellular domains of TNFR1 and investigated the signaling pathway(s) involved in TNFR1-mediated inhibition of adipocyte differentiation. Our results show that repression of adipogenesis required the juxtamembrane and death domains and was independent of the pathways involving nuclear factor κB and neutral sphingomyelinase.
