Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway
Highlights: • Eudesmin inhibits activation sand nuclear translocation of S6K1. • Eudesmin promotes Wnt gene expression by reducing S6K1-mediated H2BS36 phosphorylation. • Eudesmin disturbs adipogenic gene expression and de novo adipocyte generation. • Eudesmin enhances myogenic and osteogenic gene expression. Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway. Eudesmin treatment inhibited activation and nuclear translocation of S6K1. Consequently, S6K1-mediated phosphorylation of H2B at serine 36 (H2BS36p) was reduced upon eudesmin treatment, further inducing the expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation. Moreover, eudesmin promoted myogenic and osteogenic gene expression in MSCs. Taken together, we found a novel small molecule, eudesmin, to block adipogenesis through down-regulation of S6K1-H2BS36p axis, followed by regulation of cell fate determination genes. This study suggests a promising therapeutic approach with eudesmin to cure obesity and metabolic diseases.