Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARgamma transcriptional activity.
Dietary soy isoflavones have been shown to favorably alter the metabolic phenotypes associated with Type 2 diabetes. However, the identification of direct targets and the underlying molecular mechanisms by which soy isoflaovones exert antidiabetic effects remain elusive. Since the insulin-sensitizing effects of thiazolidinediones, antidiabetic drugs, are mediated through activation of peroxisome proliferators-activated receptor gamma (PPARgamma), we examined the effects of daidzein and the daidzein metabolite, equol, on adipocyte differentiation and PPARgamma activation. In 3T3-L1 cells, daidzein enhanced adipocyte differentiation and PPARgamma expression in a dose-dependent manner. Daidzein also dose-dependently increased insulin-stimulated glucose uptake and the relative abundance of insulin-responsive glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS-1) mRNA. In C3H10T1/2 cells, both daidzein and equol at 1 micromol/L and higher significantly increased adipocyte differentiation and insulin-stimulated glucose uptake. Furthermore, daidzein and equol up-regulated PPARgamma-mediated transcriptional activity, and daidzein restored the PPARgamma antagonist-induced inhibition of aP2 and GLUT4 mRNA levels. Our results indicate that daidzein enhances insulin-stimulated glucose uptake in adipocytes by increasing the expression of GLUT4 and IRS-1 via the activation of PPARgamma. These data further support the recent findings that favorable effects of dietary soy isoflavones may be attributable to daidzein and its metabolite equol.
Cho
Kae Won
KW
Department of Nutrition, University of Massachusetts, Amherst, MA 01003, USA.
Lee
Ok-Hwan
OH
Banz
William J
WJ
Moustaid-Moussa
Naima
N
Shay
Neil F
NF
Kim
Young-Cheul
YC
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D060754:Equol; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D007529:Isoflavones; D047495:PPAR gamma; C495693:Slc2a4 protein, mouse; D060754:Equol; C004742:daidzein; D003847:Deoxyglucose; D005947:Glucose