title: Dietary Supplementation of Genistein Alleviates Liver Inflammation and Fibrosis Mediated by a Methionine-Choline-Deficient Diet in db/db Mice.
abstract: Nonalcoholic fatty liver disease is a complex disorder which includes simple steatosis, steatohepatitis, fibrosis and ultimately cirrhosis. Previous studies have reported that genistein, a soy phytoestrogen, attenuates steatohepatitis induced in obese and type 2 diabetic models. Here we investigated the effect of dietary genistein supplementation (0.05%) on nonalcoholic steatohepatitis (NASH) development induced by a methionine-choline-deficient (MCD) diet in db/db mice. MCD-diet-fed mice exhibited a significantly lower body weight and a higher degree of steatohepatitis with increased oxidative stress, steatosis, inflammation, stellate cell activation, and mild fibrosis. Although genistein did not inhibit hepatic steatosis, we observed that oxidative stress, endoplasmic reticulum stress, and AMP-dependent kinase inactivation were alleviated by genistein. Genistein also down-regulated the augmented gene expressions associated with hepatic inflammation and fibrosis. Therefore, these results suggest that genistein may protect MCD-diet-mediated NASH development by suppressing lipid peroxidation, inflammation, and even liver fibrosis in db/db mice.
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Na-young
authors.initials: NY
authors.lastname: Yoo
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sookyoung
authors.initials: S
authors.lastname: Jeon
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Yerim
authors.initials: Y
authors.lastname: Nam
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Youn-Jin
authors.initials: YJ
authors.lastname: Park
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sae Bom
authors.initials: SB
authors.lastname: Won
authors.affiliation: †Department of Food and Nutrition and ‡Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Young Hye
authors.initials: YH
authors.lastname: Kwon
mesh_terms: D000818:Animals; D002794:Choline / Q000032:analysis*; D004032:Diet / Q000009:adverse effects; D019587:Dietary Supplements / Q000032:analysis*; D004195:Disease Models, Animal; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000032:analysis / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D008715:Methionine; D019833:Genistein; D002794:Choline
keywords: db/db mouse; fibrosis; genistein; methionine−choline-deficient diet; nonalcoholic steatohepatitis