Objective To compare different diet-induced nonalcoholic steatohepatitis (NASH) mouse models, so as to provide a reference for NASH related study.

Method Mice were randomly divided into four groups with 10 mice in each group. NASH models were established by feeding with high-fat diet (HFD) for 24 weeks, Amylin diet for 24 weeks, and high-fat methionine- and choline-deficient diet (HFMCD) for 10 weeks, respectively. 10 mice feeding by chow diet (CD) was used as control. After feeding, body weight, liver weight, serum transaminase, liver triglyceride (TG), and liver hydroxyproline levels were measured. Fasting blood glucose and insulin tolerance test (ITT) were used to assess insulin sensitivity. Hematoxylin-eosin (H-E) staining and Sirius red staining were used to indicate pathological changes of liver.

Result The mice in HFD group had obesity and insulin resistance, mild serum transaminase, liver TG, liver hydroxyproline levels, and inflammatory changes in the liver. The mice in Amylin group occured obvious NASH accompanied with obesity and severe insulin resistance. The mice in HFMCD group had severe NASH phenotype changes in a relative short time, without obesity and insulin resistance.

Conclusion All three diet-induced mouse models show different advantages and disadvantages. NASH models induced by Amylin diet recaptures the key NASH features observed in patients.