Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice

Aims: We have recently reported that monosodium glutamate (MSG) induces severe obesity with diabetes mellitus and/or non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) in Crj:CD-1 (ICR) neonatal mice. In this study, we investigated the effects of varying the dose of MSG on the resulting obesity and diabetes mellitus. Main methods: Crj:CD-1(ICR) neonatal mice were administered MSG in one of several courses: once-daily subcutaneous injections of 2 mg/g for 5 consecutive days (2 mg/g x 5 group), a single subcutaneous injection of 4 mg/g (4 mg/g x 1 group) and once-daily subcutaneous injections of 4 mg/g for 5 consecutive days (4 mg/g x 5 group). Key findings: In all the MSG treatment groups, severe obesity developed by 29 weeks of age. The onset of diabetes mellitus and liver lesions (resembling those of human NAFLD/NASH) were observed before 54 weeks of age. The obesity, diabetes mellitus and liver lesions were most severe in the 4 mg/g x 1 group. In the 4 mg/g x 5 group, increases in body weight and body length were inhibited by MSG's severe toxicity. Significance: A single 4 mg/g dose of MSG is the most suitable as the obese model and induces not only severe obesity and diabetes mellitus, but also liver changes resembling human NAFLD/NASH. A small amount of MSG in the newborn develops obesity and the other complications without hyperphagia after a long term. (C) 2009 Elsevier Inc. All rights reserved.