Regulation of Wnt/β-Catenin Signaling by CCAT/Enhancer Binding Protein β During Adipogenesis

Activation of the Wnt/beta-catenin signaling pathway inhibits adipogenesis, while disruption of Wnt signaling leads to spontaneous adipogenesis. CCAAT/enhancer binding protein beta(C/EBP beta) is rapidly induced in early stages of adipogenesis and is responsible for transcriptional induction of two major adipogenic transcription factors, peroxisome proliferator-activated receptor gamma (PPAR gamma) and C/EBP alpha. In this study, we examined whether C/EBP beta is involved in the suppression of Wnt/beta-catenin signaling during adipogenesis. Knockdown of C/EBP beta expression not only inhibited adipogenesis but also maintained active Wnt/beta-catenin signaling, after addition of adipogenic inducers. In contrast, overexpression of C/EBP beta substantially inhibited Wnt signaling. Interestingly, our data showed that C/EBP beta is involved in the expression of Wnt10b, a major Wnt ligand in preadipocytes, even though C/EBP beta is not an essential factor to regulate Wnt10b expression during adipogenesis, and that C/EBP beta inhibits Wnt10b promoter activity by directly binding to specific regions of the promoter. These results suggest a dual function of C/EBP beta: stimulating expression of adipogenic genes and inhibiting Wnt signaling.