C/EBPα regulates SIRT1 expression during adipogenesis

SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein alpha (C/EBP alpha) during adipocyte differentiation. C/EBP alpha, but not C/EBP alpha p30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBP alpha upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBP alpha upregulated SIRT1 protein level and knockdown of C/EBP alpha led to the decrease of SIRT1 protein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBP alpha bound to the SIRT1 promoter at a consensus C/EBP alpha binding site. These data demonstrate that C/EBP alpha regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.