title: Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.
abstract: OBJECTIVE
  Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG.
  
  
  METHODS
  MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed.
  
  
  RESULTS
  The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH.
  
  
  CONCLUSIONS
  DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis.
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishida
authors.forename: Hayato
authors.initials: H
authors.lastname: Baba
authors.forename: Shu
authors.initials: S
authors.lastname: Taira
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Miwa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakajima
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Sutoh
authors.forename: Emu
authors.initials: E
authors.lastname: Oda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hokao
authors.forename: Johji
authors.initials: J
authors.lastname: Imura
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002784:Cholesterol / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced*; D005421:Flavoring Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000473:pathology; D008815:Mice, Inbred Strains; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced*; D009765:Obesity / Q000139:chemically induced*; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000009:adverse effects*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005421:Flavoring Agents; D014280:Triglycerides; D002784:Cholesterol; D012970:Sodium Glutamate
keywords: DIAR mice; liver nodules; macrovesicular steatosis; monosodium glutamate; non-alcoholic steatohepatitis; obesity; type 2 diabetes