Tumour necrosis factor- α inhibits adipogenesis via a β -catenin/TCF4(TCF7L2)-dependent pathway

摘要: Tumour necrosis factor-α (TNF-α), a proinflammatory cytokine, is potent negative regulator of adipocyte differentiation. However, the mechanism TNF-α-mediated antiadipogenesis remains incompletely understood. In this study, we first confirm that TNF-α inhibits adipogenesis 3T3-L1 preadipocytes by preventing early induction adipogenic transcription factors peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα). This suppression coincides with enhanced expression several reported mediators are also targets Wnt/β-catenin/T-cell factor 4 (TCF4) pathway. Indeed, found TCF4-dependent transcriptional activity during antiadipogenesis, promoted stabilisation β-catenin throughout antiadipogenesis. We analysed effect on in cells which β-catenin/TCF signalling was impaired, either via stable knockdown β-catenin, or overexpression dominant-negative TCF4 (dnTCF4). The potential attenuated TNF-α-induced apoptosis these cells. contrast, dnTCF4 prevented but showed no apparent cell survival. Finally, show requires functional death domain receptor 1 (TNFR1). Taken together data suggest TNFR1-mediated signals can inhibit β-catenin/TCF4-dependent