Influence of age in weeks on the development and progression of nonalcoholic steatohepatitis in a diet-induced Sprague-Dawley rat model

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  • Omagari Katsuhisa
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Yamasaki Mayu
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Linh Chi Thi Ngo
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Koba Chiaki
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Nagata Asuka
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Fukuda Ayumi
    Division of Nutrition Science, Graduate School of Human Health Science, University of Nagasaki
  • Suruga Kazuhito
    Department of Nutritional Science, Faculty of Nursing and Nutrition, University of Nagasaki
  • Ichimura-Shimizu Mayuko
    Department of Pathology and Laboratory Medicine, Tokushima University Graduate School
  • Tsuneyama Koichi
    Department of Pathology and Laboratory Medicine, Tokushima University Graduate School

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Background: Understanding the pathogenesis of nonalcoholic steatohepatitis (NASH) in humans has been hampered by the lack of a comprehensive and physiological small animal model of NASH. We previously reported a dietary (high-fat and high-cholesterol; HFC diet) -induced NASH model that developed advanced fibrosis within a relatively short period (9 weeks) using Sprague-Dawley (SD) rats (age, 9 weeks). Methods: In this study, we evaluated the age-related alterations of NASH in 9-, 18-, and 27-week-old male SD rats that were fed an HFC diet (30% fat, 1.25% cholesterol, and 0.5% sodium cholate, w/w) for 9 weeks (six rats/group). Results: Age-dependent increases in serum transaminases, insulin, and insulin resistance index were observed with or without a significant difference after the 9-week rearing period. Histopathological findings such as hepatic steatosis, lobular inflammation, and hepatocyte ballooning were similar regardless of age, but hepatic fibrosis was more evident in the older groups. Rats in all three groups developed NASH at a high rate (83.3% or higher in each group). The mRNA levels of fibrosis-related genes encoding transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) in the liver were low in the youngest group and high in the older groups, although this difference was not statistically significant. Conclusion: These results and those from our previous study indicate that a 9-week HFC diet-induced NASH model using SD rats can be applied a relatively wide range of ages (5-27 weeks of old), and that the risk of NASH-related fibrosis increases with age.

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