To date, we have established a non-alcoholic steatohepatitis (NASH) model by feeding rats and mice a choline-deficient amino acid diet or a high-fat diet. However, it has been pointed out that it takes a long time to prepare the model and that the extrapolation to humans is low. Therefore, we confirmed the reproducibility of the NASH model, which develops in a short period of time, by referring to the method of Ohkohchi et al., and whether bezafibrate is effective for this model.
　C57BL/6J mice were fed a high-fat diet (60 kcal% fat, HF) for 4 weeks. The NASH model was constructed by administering carbon tetrachloride twice a week from 2 weeks after the start of HF loading and T0901317 during the last 5 days of HF loading. Bezafibrate was administered orally for 4 weeks from the start of HF loading. On the last day of HF loading, blood was collected and the liver was removed, and an insulin resistance test was performed. Serum AST, ALT, and TG levels and the amount of hydroxyproline in the liver were measured, and the liver was examined histopathologically.
　Administration of carbon tetrachloride and T0901317 during a 4-week high-fat loading induced hepatic steatosis and fibrosis, confirming the reproducibility of the NASH model. Bezafibrate inhibited hepatic steatosis and fibrosis, and showed efficacy against NASH.