A metabolite of daidzein, 6,7,4 '-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K

作者：Seo Sang Gwon; Yang Hee; Shin Seung Ho; Min Soyun; Kim Yeong A; Yu Jae Gak; Lee Dong Eun; Chung Min Yu; Heo Yong Seok; Kwon Jung Yeon; Yue Shuhua; Kim Kee Hong; Cheng Ji Xin; Lee Ki Won; Lee Hyong Joo^*

来源：Molecular Nutrition & Food Research, 2013, 57(8): 1446-1455.

DOI：10.1002/mnfr.201200593

• Adipogenesis
• Daidzein
• PI3K
• 3
• 6
• 7
• 4-

Scope: Daidzein is one of the major soy isoflavones. Following ingestion, daidzein is readily metabolized in the liver and converted into hydroxylated metabolites. One such metabolite is 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), which has been the focus of recent studies due to its various health benefits, however, its anti-adipogenic activity has not been investigated. Our objective was to determine the effects of 6,7,4'-THIF on adipogenesis in 3T3-L1 preadipocytes and elucidate the mechanisms of action involved.
Methods and results: Adipogenesis was stimulated in 3T3-L1 preadipocytes. Both 6,7,4'-THIF and daidzein were treated in the presence and absence of mixture of isobutylmethylxanthine, dexamethasone, and insulin (MDI). We observed that 6,7,4'-THIF, but not daidzein, inhibited MDI-induced adipogenesis significantly at 40 and 80 mu M, associated with decreased peroxisome proliferator-activated receptor-gamma and C/EBP-alpha protein expression. 6,7,4'-THIF significantly suppressed MDI-induced lipid accumulation in the early stage of adipogenesis, attributable to a suppression of cell proliferation and the induction of cell cycle arrest. We also determined that 6,7,4'-THIF, but not daidzein, attenuated phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. 6,7,4'-THIF was found to inhibit PI3K activity via direct binding in an ATP-competitive manner.
Conclusion: Our results suggest that 6,7,4'-THIF suppresses adipogenesis in 3T3-L1 preadipocytes by directly targeting PI3K. Soy isoflavones like 6,7,4'-THIF may have potential for development into novel treatment strategies for chronic obesity.

• 出版日期2013-8