TitleA metabolite of daidzein, 6,7,4'-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K.
Publication TypeJournal Article
Year of Publication2013
AuthorsSeo, SGwon, Yang, H, Shin, SHo, Min, S, Kim, YA, Yu, JGak, Lee, DEun, Chung, M-Y, Heo, Y-S, Kwon, JYeon, Yue, S, Kim, KHong, Cheng, J-X, Lee, KWon, Lee, HJoo
JournalMol Nutr Food Res
Volume57
Issue8
Pagination1446-55
Date Published2013 Aug
ISSN1613-4133
Keywords3T3-L1 Cells, Adenosine Triphosphate, Adipogenesis, Animals, Binding, Competitive, CCAAT-Enhancer-Binding Protein-alpha, Cell Cycle, Cell Proliferation, Dexamethasone, Down-Regulation, Enzyme Inhibitors, Insulin, Isoflavones, Mice, Phosphatidylinositol 3-Kinases, Phosphorylation, PPAR gamma, Proto-Oncogene Proteins c-akt
Abstract

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 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.

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.

DOI10.1002/mnfr.201200593
Alternate JournalMol Nutr Food Res
PubMed ID23737351