Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway

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• 作者：Haeyong Lee^a ; Sungmin Bae^a ; Kijeong Kim^a ; Wonyong Kim^a ; Sang-In Chung^a ; Young Yang^b ; Yoosik Yoon^a ; ^{thanks@cau.ac.kr}
• 关键词：Shikonin ; Adipogenesis ; WNT ; β ; -catenin ; 3T3-L1
• 刊名：Life Sciences
• 出版年：2011
• 出版时间：14 February 2011
• 年：2011
• 卷：88
• 期：7-8
• 页码：294-301
• 全文大小：1296 K

文摘

Aim

Our previous study showed for the first time that shikonin, a natural compound isolated from Lithospermun erythrorhizon Sieb. Et Zucc, inhibits adipogenesis and fat accumulation. This study was conducted to investigate the molecular mechanism of the anti-adipogenic effects of shikonin.

Main methods

Gene knockdown experiments using small interfering RNA (siRNA) transfection were conducted to elucidate the crucial role of β-catenin in the anti-adipogenic effects of shikonin.

Key findings

Shikonin prevented the down-regulation of β-catenin and increased the level of its transcriptional product, cyclin D1, during adipogenesis of 3T3-L1 cells, preadipocytes originally derived from mouse embryo. β-catenin was a crucial mediator of the anti-adipogenic effects of shikonin, as determined by siRNA-mediated knockdown. Shikonin-induced reductions of the major transcription factors of adipogenesis including peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α, and lipid metabolizing enzymes including fatty acid binding protein 4 and lipoprotein lipase, as well as intracellular fat accumulation, were all significantly recovered by siRNA-mediated knockdown of β-catenin. Among the genes located in the WNT/β-catenin pathway, the levels of WNT10B and DVL2 were significantly up-regulated, whereas the level of AXIN was down-regulated by shikonin treatment.

Significance

This study clearly shows that shikonin inhibits adipogenesis by the modulation of WNT/β-catenin pathway in vitro, and also suggests that WNT/β-catenin pathway can be used as a therapeutic target for obesity and related diseases using a natural compound like shikonin, even though the in vivo effects of shikonin and its clinical significance remain to be elucidated.