|Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARgamma transcriptional activity.
|Year of Publication
|Cho, KWon, Lee, O-H, Banz, WJ, Moustaid-Moussa, N, Shay, NF, Kim, Y-C
|J Nutr Biochem
|3T3-L1 Cells, Adipocytes, Animals, Cell Differentiation, Deoxyglucose, Equol, Fatty Acid-Binding Proteins, Glucose, Glucose Transporter Type 4, Insulin Receptor Substrate Proteins, Isoflavones, Mice, PPAR gamma
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.
|J. Nutr. Biochem.