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KMID : 0545120120220060806
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 6 p.806 ~ p.813
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Widdrol Blocks 3T3-L1 Preadipocytes Growth and Differentiation Due to Inhibition of Mitotic Clonal Expansion
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Yun Hee-Jung
Kim Jeong-Hwan
Jeong Hyun-Young
Ji Hyang-Hwa
Nam Soo-Wan
Lee Eun-Woo
Kim Byung-Woo
Kwon Hyun-Ju
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Abstract
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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/EBPα, C/EBPβ, and PPARγ. 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.
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KEYWORD
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Adipocyte differentiation, anti-obesity, mitotic clonal expansion, widdrol, 3T3-L1 preadipocyte
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