title: Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome.
abstract: Recently, we reported that monosodium glutamate-treated mice (MSG mice) developed severe hyperlipidemia and diabetes mellitus and several complications of obesity. MSG mice acquired fatty livers and subsequently underwent changes that are characteristic of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). In the present study, the effects of bezafibrate on obesity, diabetes mellitus, and NAFLD/NASH were examined in MSG mice. A single dose of MSG (4 mg/g) was administered subcutaneously to neonatal male mice within 24h of birth. Bezafibrate was mixed into the normal feed for 8 weeks. The weight and body mass index of MSG mice increased significantly despite the unchanged intake of food. Triglyceride and total cholesterol levels in blood, visceral adipose tissue, and interscapular adipose tissue rose significantly. In the livers of MSG mice, moderate centrilobular microvesicular steatosis, ballooning degeneration with Mallory bodies, and scattered infiltration of neutrophils and lymphocytes were observed. Centrilobular hepatocytes were 4-hydroxynonenal-positive in MSG mice. Bezafibrate ameliorated the severity of diabetes mellitus, hyperinsulinemia, and hyperlipidemia. Adiponectin and leptin concentrations in blood improved, and the accumulation of visceral fat was inhibited. The expression of acyl-CoA oxidase, a beta-oxidation gene, and carnitine palmitoyl transferase, which regulates lipid metabolism, increased markedly on administration of bezafibrate. The liver pathology in MSG mice also improved with bezafibrate; specifically, macro- and microvesicles in hepatocytes nearly disappeared, and NAFLD activity score improved. It is concluded that bezafibrate inhibits the accumulation of visceral fat, following amelioration of hyperlipidemia, in MSG-induced obese mice, due to improvements in diabetes mellitus, fatty liver, and NAFLD.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo-shi, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.forename: Seiichi
authors.initials: S
authors.lastname: Iizuka
authors.forename: Wataru
authors.initials: W
authors.lastname: Suzuki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Makihara
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Teraoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hokao
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology* / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006029:Glycosuria / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012970:Sodium Glutamate / Q000494:pharmacology*
chemical_list: D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D012970:Sodium Glutamate; D001629:Bezafibrate