Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARgamma transcriptional activity

J Nutr Biochem. 2010 Sep;21(9):841-7. doi: 10.1016/j.jnutbio.2009.06.012. Epub 2009 Sep 22.


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.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Animals
  • Cell Differentiation / drug effects
  • Deoxyglucose / metabolism
  • Equol
  • Fatty Acid-Binding Proteins / biosynthesis
  • Glucose / metabolism
  • Glucose Transporter Type 4 / biosynthesis
  • Insulin Receptor Substrate Proteins / biosynthesis
  • Isoflavones / pharmacology*
  • Mice
  • PPAR gamma / metabolism*


  • 4',7-dihydroxy-3,4-dihydroisoflavone
  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Glucose Transporter Type 4
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Isoflavones
  • PPAR gamma
  • Slc2a4 protein, mouse
  • Equol
  • daidzein
  • Deoxyglucose
  • Glucose