Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE―/― mice fed a high-fat diet
Version of Record online: 11 NOV 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 4, pages 830–841, April 2014
How to Cite
Jeon, S., Park, Y.-J. and Kwon, Y. H. (2014), Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE―/― mice fed a high-fat diet. Mol. Nutr. Food Res., 58: 830–841. doi: 10.1002/mnfr.201300112
- Issue online: 1 APR 2014
- Version of Record online: 11 NOV 2013
- Manuscript Accepted: 26 AUG 2013
- Manuscript Revised: 23 AUG 2013
- Manuscript Received: 7 FEB 2013
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology. Grant Number: #2009-0069120 and #2012-014736
- ApoE―/― mouse;
- Lipid peroxidation;
- Nonalcoholic steatohepatitis
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.
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.