| Autor: |
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 |
| Předmět: |
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| Zdroj: |
Diabetes; Dec2018, Vol. 67 Issue 12, p2569-2584, 16p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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