Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARγ 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 (PPAR gamma), we examined the effects of daidzein and the daidzein metabolite, equol, on adipocyte differentiation and PPAR gamma activation In 3T3-L1 cells, daidzein enhanced adipocyte differentiation and PPAR gamma 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 mu mol/L and higher significantly Increased adipocyte differentiation and insulin-stimulated glucose uptake. Furthermore, daidzein and equol up-regulated PPAR gamma-mediated transcriptional activity, and daidzein restored the PPAR gamma 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 PPAR gamma. These data further support the recent findings that favorable effects of dietary soy isoflavones may be attributable to daidzein and its metabolite equol Published by Elsevier Inc.