Neonatal MSG Treatment in DIAR Mice Causes Macrovesicular Steatosis with Lobular Inflammation in the Liver
Takeshi Nishida, Koichi Tsuneyama, Kazuhiro Nomoto, Shinichi Hayashi, Shigeharu Miwa, Takahiko Nakajima, Yuko Nakanishi, Yoshiyuki Sasaki, Satoko Nakamura, Ryoji Hokao, Johji Imura. University of Toyama, Toyama, Japan; Institute for Animal Reproduction, Kasumigaura, Ibaraki, Japan
Background: The liver manifestations of metabolic syndrome include non-alcoholic fatty liver disease and its progressive variant, non-alcoholic steatohepatitis (NASH). Centrilobular macrovesicular steatosis is one of the typical pathological findings of NASH. We have previously reported that subcutaneous injection of monosodium glutamate (MSG) in neonatal ICR mice resulted in NASH-like pathology. However, its steatosis was microvesicular. DIAR mice are an inbred strain selected from ddy for their non-diabetic features. In a preliminary study, DIAR mice spontaneously developed sporadic macrovesicular steatosis. With an aim to develop a NASH mouse model with macrovesicular steatosis, we analyzed the liver pathology and other characteristic findings of DIAR mice following neonatal MSG treatment.
Design: Twenty-nine- and 54-week-old MSG-treated (DIAR-MSG) and MSG-untreated (DIAR-control) male mice were analyzed. Each group contained 5-6 mice. Liver was removed and fixed in 10% formalin. The specimens were evaluated by hematoxylin-eosin staining, silver staining, and Azan staining. NASH activity scores and the type of steatosis were evaluated. Measurement of body mass index (BMI) and blood glucose level, and oral glucose tolerance test (OGTT) were performed for mice aged 29 weeks.
Results: BMI and blood glucose levels of DIAR-MSG mice were significantly higher than those of DIAR-control mice. OGTT revealed a type 2 diabetes pattern in DIAR-MSG mice. The liver of 29-week-old DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration.
At age 54 weeks, mild perivenular and pericellular fibrosis were observed in 83% of DIAR-MSG mice. Some mice exhibited cellular and structural atypia, mimicking human hepatocellular carcinoma.
Conclusions: DIAR-MSG mice exhibited mild obesity and type 2 diabetes. In addition, these mice exhibited macrovesicular steatosis, lobular inflammation, ballooning degeneration, and mild perivenular fibrosis of the liver. In 54-week-old mice, atypical liver nodules were also observed frequently. These findings are quite similar to those of human NASH. In conclusion, DIAR-MSG mice are a valuable animal model to evaluate NASH pathogenesis and carcinogenesis.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 150, Tuesday Afternoon