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- Title
Pygo2 Regulates Adiposity and Glucose Homeostasis via β-Catenin-Axin2-GSK3β Signaling Pathway.
- Authors
Yuan-Yuan Xie; Chun-Li Mo; Yi-Huang Cai; Wen-Jie Wang; Xin-Xin Hong; Kun-Kun Zhang; Qing-Feng Liu; Yun-Jia Liu; Jing-Jing Hong; Ting He; Zhong-Zheng Zheng; Wei Mo; Bo-An Li; Xie, Yuan-Yuan; Mo, Chun-Li; Cai, Yi-Huang; Wang, Wen-Jie; Hong, Xin-Xin; Zhang, Kun-Kun; Liu, Qing-Feng
- Abstract
Wnt/β-catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of C/EBPα and peroxisome proliferator-activated receptor γ (PPARγ); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/β-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/β-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 GSK3β was released and translocated into the nucleus to phosphorylate C/EBPβ and Snail, resulting in an increase in the DNA binding activity of C/EBPβ and decreased protein stability of Snail, which subsequently activated the expression of C/EBPα and PPARγ. 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.
- Subjects
CATENINS; ADIPOGENESIS; PEROXISOME proliferator-activated receptors; MOLECULAR mechanisms of immunosuppression; OBESITY; DNA-binding proteins
- Publication
Diabetes, 2018, Vol 67, Issue 12, p2569
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db18-0311