S-Adenosylmethionine-induced adipogenesis is accompanied by suppression of Wnt/β-catenin and Hedgehog signaling pathways

S-Adenosylmethionine (SAM) plays a crucial role as a methyl donor in various biological processes and has been previously shown to be involved in adipogenesis in skeletal muscle. This study was conducted to explore the mechanism of SAM inducing adipogenesis in skeletal muscle. Adipose precursor cells, 3T3-L1, and C2C12 cells, were induced into adipogenic differentiation by addition of SAM in MDI-differentiation media (0.5 mmol/L isobutylmethylxanthine, 1 mu m/L dexamethasone, and 10 mu g/mL insulin) to explore the role of SAM in promoting adipogenesis. Subsequently, cells were cultured with a medium containing SAM alone at the beginning of differentiation to test the relationship between SAM-induced adipogenesis and Wnt/beta-catenin, and Hedgehog signaling pathways that control the cell commitment to adipogenic- or myogenic-differentiation. We found SAM possessed an additive effect with MDI in promoting adipogenesis of 3T3-L1 and C2C12 cells at the beginning of adipogenic differentiation. SAM could also individually induce cell adipogenesis in a dose-dependent manner. Moreover, the expression of Wnt/beta-catenin and Hedgehog signals and their targets were suppressed by SAM (P < 0.05). These results demonstrate that SAM, as an increasingly accepted nutritional supplement, can initiate adipogenesis of adipose precursor cells derived from adipose and muscle tissues, a function at least partly correlated with the suppression of Wnt/beta-catenin and Hedgehog pathways.