An essential role for Ewing sarcoma gene (EWS) in early white adipogenesis

Objective White adipose tissue is important for mammalian energy homeostasis and metabolism. It was previously demonstrated that Ewing sarcoma gene (EWS) is essential for early classical brown fat lineage determination, but its role in white adipocyte differentiation is not known. Methods Mouse embryonic fibroblasts (MEFs) lacking Ews and shRNA-mediated silencing of Ews in 3T3L1 preadipocytes were used to investigate the role of EWS in adipogenesis. White fat differentiation was determined by analyzing the expression of key adipogenic genes and by Oil red O staining. Results Following adipogenic stimulation, Ews expression arose rapidly in 3T3L1 cells during early induction period. Ews-null MEFs and 3T3L1 cells with reduced Ews expression failed to undergo adipogenesis. This was accompanied by significant reduction in the expression of critical early adipogenic regulators, Bmp2, Bmp4 (bone morphogenic protein 2 and 4), Cebpβ, and Cebpδ (CCAAT/enhancer binding protein β and δ). Complementation of recombinant BMP2 or BMP4 partially rescued adipogenesis in Ews-depleted 3T3L1 cells. Conclusions These results demonstrate that EWS is essential during the early steps of white adipocyte differentiation, at least in part through its regulation of BMP2 and BMP4 expression.