Dose dependent development of diabetes mellitus and non-alcoholic steatohepatitis in monosodium glutamate-induced obese mice.
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.
Sasaki
Yoshiyuki
Y
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.
Suzuki
Wataru
W
Shimada
Tsutomu
T
Iizuka
Seiichi
S
Nakamura
Satoko
S
Nagata
Mitsunobu
M
Fujimoto
Makoto
M
Tsuneyama
Koichi
K
Hokao
Ryoji
R
Miyamoto
Ken-Ichi
K
Aburada
Masaki
M
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*
D005503:Food Additives; D005947:Glucose; D012970:Sodium Glutamate