HMGB2 orchestrates mitotic clonal expansion by binding to the promoter of CCAAT-enhancer binding protein beta to facilitate adipogenesis

High-mobility group box 2 (HMGB2) is abundantly expressed during embryogenesis and implicated in cell proliferation, differentiation, transcription, and tumorigenesis, which has been reported as a novel adipogenic factor. However, the roles and underlying mechanisms of HMGB2 in adipogenesis remain to be further elucidated. Here, we show that HMGB2 deficiency in preadipocytes impedes their adipogenesis, while overexpression of HMGB2 increases the potential for adipogenic differentiation. Besides, the stromal vascular fraction (SVF) of adipose tissue derived from HMGB2-/- mice exhibit reduced adipogenesis. Further, depletion of HMGB2 in vivo decreases adipose tissue weight. The attenuated adipogenesis of HMGB2-/- mice can be rescued when fed a high-fat diet. HMGB2 influences adipogenesis by regulating mitotic clonal expansion, one of the early adipogenic differentiation events. Mechanistically, HMGB2 binds to the promoter of CCAAT-enhancer binding and promotes the expression of CCAAT-enhancer binding protein beta during mitotic clonal expansion to facilitate adipogenesis. Together, our findings uncover a critical role of HMGB2 in adipogenesis and provide potential therapeutic targets for obesity.