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Keywords:

  • ApoE―/― mouse;
  • Genistein;
  • Hypercholesterolemia;
  • Lipid peroxidation;
  • Nonalcoholic steatohepatitis

Scope

Genistein (GEN) is a compound that has been shown to alleviate hepatic steatosis. Here, we investigated its protective effects against non-alcoholic steatohepatitis (NASH) development in apolipoprotein E-deficient (ApoE―/―) mice fed a high-fat diet (HFD).

Methods and results

Wild-type and ApoE―/― mice were fed an HFD with or without GEN (0.5 g/kg diet) for 24 weeks. Body weights were reduced and fecal cholesterol excretion was increased by GEN. GEN supplementation lowered serum and hepatic cholesterol and lipid peroxidation levels, and hepatic heme oxygenase 1 protein levels in ApoE―/― mice. Hepatic expressions of scavenger receptors involved in oxidized LDL uptake, CD36 and scavenger receptor A, were downregulated by GEN. GEN reduced serum alanine aminotransferase and monocyte chemoattractant protein 1 levels, and hepatic nuclear factor-κB-mediated inflammatory gene expressions in ApoE―/― mice. These levels were higher in ApoE―/― mice fed an HFD than their corresponding wild-type mice. GEN also alleviated hepatic steatosis by reducing mRNA levels of monoacylglycerol O-acyltransferase 1, a target gene of peroxisome proliferator-activated receptor γ.

Conclusion

GEN alleviated NASH as well as hypercholesterolemia and obesity in ApoE―/― mice fed an HFD. Restoration of altered cholesterol metabolism and oxidative stress may be involved in the protective effect of GEN against NASH development.