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

Abstract

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.

• Authors: Kae Won Cho, Ok-Hwan Lee, William J Banz, Naima Moustaid-Moussa, Neil F Shay, Young-Cheul Kim
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 21 Issue 9 Pg. 841-7 (Sep 2010) ISSN: 1873-4847 [Electronic] United States
• PMID: 19775880 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Inc.

Chemical References

• 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

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, 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)