دورية أكاديمية

Pygo2 Regulates Adiposity and Glucose Homeostasis via β-Catenin-Axin2-GSK3β Signaling Pathway.

التفاصيل البيبلوغرافية
العنوان: Pygo2 Regulates Adiposity and Glucose Homeostasis via β-Catenin-Axin2-GSK3β Signaling Pathway.
المؤلفون: 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
المصدر: Diabetes; Dec2018, Vol. 67 Issue 12, p2569-2584, 16p
مصطلحات موضوعية: CATENINS, ADIPOGENESIS, PEROXISOME proliferator-activated receptors, MOLECULAR mechanisms of immunosuppression, OBESITY, DNA-binding proteins
مستخلص: 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]
Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:00121797
DOI:10.2337/db18-0311