title: Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Crj:CD-1(ICR) neonatal mice were administered MSG in one of several courses: once-daily subcutaneous injections of 2mg/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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, and Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Suzuki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.forename: Seiichi
authors.initials: S
authors.lastname: Iizuka
authors.forename: Satoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Nagata
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hokao
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015992:Body Mass Index; D001835:Body Weight; D003920:Diabetes Mellitus / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005503:Food Additives / Q000494:pharmacology*; D005947:Glucose / Q000032:analysis; D008099:Liver / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008820:Mice, Obese; D012970:Sodium Glutamate / Q000494:pharmacology*
chemical_list: D005503:Food Additives; D005947:Glucose; D012970:Sodium Glutamate