| First Author | Xie YY | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 12 | Pages | 2569-2584 |
| PubMed ID | 30279163 | Mgi Jnum | J:267720 |
| Mgi Id | MGI:6258087 | Doi | 10.2337/db18-0311 |
| Citation | Xie YY, et al. (2018) Pygo2 Regulates Adiposity and Glucose Homeostasis via beta-Catenin-Axin2-GSK3beta Signaling Pathway. Diabetes 67(12):2569-2584 |
| abstractText | Wnt/beta-catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/beta-catenin output level during adipogenesis is also not completely defined. In this study, we showed that Pygo2 exhibited a declined expression pattern during adipocyte differentiation, resulting in an attenuated Wnt/beta-catenin output level. The mechanism study indicated that Pygo2 inhibition led to the downregulation of Axin2, a constitutive Wnt target, in the cytoplasm. Consequently, Axin2-bound GSK3beta was released and translocated into the nucleus to phosphorylate C/EBPbeta and Snail, resulting in an increase in the DNA binding activity of C/EBPbeta and decreased protein stability of Snail, which subsequently activated the expression of C/EBPalpha and PPARgamma. Consistent with this, embryonic fibroblasts from Pygo2(-/-) mice exhibited spontaneous adipocyte differentiation, and adipocyte precursor-specific Pygo2-deficient mice exhibited increased adiposity with decreased energy expenditure. We further showed impaired glucose tolerance and decreased systemic insulin sensitivity in Pygo2-deficient mice. Our study revealed an association between Pygo2 function and obesity or diabetes. |
