Transcriptional Regulation of TCF/LEF and PPARγ by Daidzein and Genistein in 3T3-L1 Preadipocytes.

Abstract

Adipogenesis is central to adipose tissue plasticity and lipid homeostasis. Regulation of adipogenic signaling by phytoestrogens has been implicated as a potential therapeutic strategy for obesity-related disease. However, it remains unclear how these compounds directly impact transcriptional control of adipogenesis. As such, the focus of this study was to determine how daidzein and genistein effect transcriptional activation of peroxisome proliferator-activated receptor gamma (PPARγ) and TCF/LEF in 3T3-L1 preadipocytes. We also measured the effect of estrogen receptor (ER) knockdown on expression of preadipocyte (i.e., Pref1) and adipocyte (i.e., Fabp4) markers in cells treated with varying concentrations of daidzein or genistein (i.e., 10-4, 10-7, and 10-10). Our findings showed that activation of TCF/LEF was induced by daidzein and genistein in undifferentiated and differentiated 3T3-L1 preadipocytes. Conversely, PPARγ reporter activity was inhibited by genistein, which corresponded with a reduction in cell diameter of differentiated preadipocytes. Daidzein increased cell diameter, as well as reduced Pref1 abundance in undifferentiated cells. Although small, there was a significant reduction in Pref1 and Fabp4 abundance in undifferentiated cells with ERα and ERβ knockdown. However, reduced abundance of ER subtypes exhibited no significant effect on phytoestrogen treatment. Collectively, our findings show phytoestrogens distinctly regulate adipogenic transcription factors and thus, may have implications for adipose dysfunction and obesity-related disease.