Regulating the Balance between Peroxisome Proliferator-activated Receptor γ and β-Catenin Signaling during Adipogenesis A GLYCOGEN SYNTHASE KINASE 3β PHOSPHORYLATION-DEFECTIVE MUTANT OF β-CATENIN INHIBITS EXPRESSION OF A SUBSET OF ADIPOGENIC GENES

摘要: The differentiation of preadipocytes into adipocytes requires the suppression canonical Wnt signaling, which appears to involve a peroxisome proliferator-activated receptor γ (PPARγ)-associated targeting β-catenin proteasome. In fact, sustained activation by expression Wnt1 or 10b in blocks adipogenesis inhibiting PPARγ-associated gene expression. this report, we investigated mechanisms regulating balance between and PPARγ signaling that determines whether mouse fibroblasts differentiate adipocytes. Specifically, show exposure Swiss troglitazone stimulates degradation β-catenin, depends on glycogen synthase kinase (GSK) 3β activity. Mutation serine 37 (a target GSK3β) an alanine renders resistant degradatory action PPARγ. Ectopic GSK3β phosphorylation-defective S37A-β-catenin expressing pathway without blocking their troglitazone-dependent lipid-laden cells. Analysis protein these cells, however, shows inhibits select set adipogenic genes because adiponectin is completely blocked, but FABP4/aP2 unaffected. Furthermore, mutant have no affect ability bind transactivate PPAR response element. S37A-β-catenin-associated inhibition coincides with extensive decrease abundance C/EBPα nuclei differentiated fibroblasts. Taken together, data suggest GSKβ key regulator activity downstream subset genes.