Widdrol blocks 3T3-L1 preadipocytes growth and differentiation due to inhibition of mitotic clonal expansion

Journal of Microbiology and Biotechnology
Hee Jung YunHyun Ju Kwon

Abstract

Adipocyte differentiation is strongly associated with obesity, which causes metabolic disorders. In this study, we investigated the inhibitory effects of widdrol on 3T3- L1 preadipocyte growth and differentiation. Widdrol decreased lipid droplet accumulation and down-regulated adipogenic transcription factors such as C/EBPalpha, C/EBPbeta, and PPARgamma. Widdrol blocked preadipocyte proliferation and differentiation through the inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor. Cell-cycle analysis clearly indicated that widdrol actively induces cell-cycle arrest at the G1-S phage transition, causing cells to remain in the preadipocyte state. Moreover, widdrol increased p21 expression and inhibited Rb phosphorylation in preadipocyte incubated in a hormone medium. Therefore, these findings clearly suggest that widdrol blocks preadipocyte growth and differentiation through the inhibition of mitotic clonal expansion by p21- and Rb-dependent G1 arrest and can be developed as a potent anti-adipogenic agent for reducing obesity.

Citations

Sep 12, 2015·Molecular and Cellular Biochemistry·Hyun Young JeongHyun Ju Kwon
Mar 22, 2014·Journal of Lipid Research·Salil VarshneyAnil Nilkanth Gaikwad
Jun 9, 2018·International Journal of Molecular Sciences·Hyejin LeeJae-Ha Ryu
Mar 19, 2014·International Journal of Food Sciences and Nutrition·Yuxuan PengZhonghua Liu

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