Genistein alleviates the development of nonalcoholic steatohepatitis in ApoE(-/-) mice fed a high-fat diet.
METHODS
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).


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.


CONCLUSIONS
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.
Department of Food and Nutrition, Seoul National University, Seoul, Korea.
Sookyoung
S
Jeon
Youn-Jin
YJ
Park
Young Hye
YH
Kwon
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D019833:Genistein / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017351:N-Acetylglucosaminyltransferases; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D019833:Genistein; D000217:Acyltransferases; C459903:MGAT1 protein, mouse; D017351:N-Acetylglucosaminyltransferases
ApoE―/― mouse; Genistein; Hypercholesterolemia; Lipid peroxidation; Nonalcoholic steatohepatitis