A metabolite of daidzein, 6,7,4′-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K
Article first published online: 4 JUN 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Lipidomics: Approaches and Applications in Nutrition Research
Volume 57, Issue 8, pages 1446–1455, August 2013
How to Cite
Seo, S. G., Yang, H., Shin, S. H., Min, S., Kim, Y. A., Yu, J. G., Lee, D. E., Chung, M.-Y., Heo, Y.-S., Kwon, J. Y., Yue, S., Kim, K. H., Cheng, J.-X., Lee, K. W. and Lee, H. J. (2013), A metabolite of daidzein, 6,7,4′-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K. Mol. Nutr. Food Res., 57: 1446–1455. doi: 10.1002/mnfr.201200593
- Issue published online: 2 AUG 2013
- Article first published online: 4 JUN 2013
- Manuscript Accepted: 19 FEB 2013
- Manuscript Revised: 16 FEB 2013
- Manuscript Received: 7 SEP 2012
- National Research Foundation of Korea (NRF)
- Korea government. Grant Numbers: 2010–0029233, 2010–0027204
- Next-Generation BioGreen 21 Program. Grant Number: PJ008060
- 3T3-L1 preadipocytes;
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 μM, associated with decreased peroxisome proliferator-activated receptor-γ and C/EBP-α 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.
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.