title: A metabolite of daidzein, 6,7,4'-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sang Gwon
authors.initials: SG
authors.lastname: Seo
authors.forename: Hee
authors.initials: H
authors.lastname: Yang
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Shin
authors.forename: Soyun
authors.initials: S
authors.lastname: Min
authors.forename: Yeong A
authors.initials: YA
authors.lastname: Kim
authors.forename: Jae Gak
authors.initials: JG
authors.lastname: Yu
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Lee
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chung
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kwon
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yue
authors.forename: Kee Hong
authors.initials: KH
authors.lastname: Kim
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Cheng
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001667:Binding, Competitive; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D022763:CCAAT-Enhancer-Binding Protein-alpha; D003907:Dexamethasone; D004791:Enzyme Inhibitors; D007328:Insulin; D007529:Isoflavones; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C502164:6,7,4'-trihydroxyisoflavone; C004742:daidzein
keywords: 3T3-L1 preadipocytes; 6,7,4′-THIF; Adipogenesis; Daidzein; PI3K