Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells

Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor beta (ER beta) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ER beta antagonist were treated with HepG2 cells. Results showed that 25 mu M GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid beta-oxidation, such as carnitine palmitoyltransferase 1 alpha (CPT-1 alpha) and peroxisome proliferator-activated receptor alpha (PPAR alpha). Furthermore, 25 mu M GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ER beta. In conclusion, GEN improved hepatic lipid metabolism by activating ER beta and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ER beta on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.

Automated summary

GEN can improve hepatic lipid metabolism by activating ERβ and modulating the signals of protein kinases, leading to reduced lipogenesis. These findings provide novel insights into the regulatory mechanism of ERβ in hepatic lipid metabolism and may help to further understand the role of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.