Monosodium glutamate is used to induce metabolic syndrome in a rat model.

Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome.

Yosuke Sasaki, Tsutomu Shimada, Seiichi Iizuka, Wataru Suzuki, Hiroko Makihara, Ryutaro Teraoka, Koichi Tsuneyama, Ryoji Hokao, Masaki Aburada

Eur J Pharmacol

Jul 15, 2011

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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 (4mg/g) was administered subcutaneously to neonatal male mice within 24h of birth. Bezafibrate was mixed into the normal feed for 8weeks. 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.

Affiliation

Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan; Institute for Animal Reproduction, 1103 Fukaya, Kasumigaura-shi, Ibaraki 300-0134, Japan.