Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 25, Issue 33, Pages 4904-4920Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v25.i33.4904
Keywords
Non-alcoholic steatohepatitis; High-fat diet; Mouse model; Histopathology; Fibrosis; Liver biopsy; Liver transcriptome
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Funding
- Innovation Fund Denmark [5016-00168B]
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BACKGROUND The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/64 mice with or without the Lep(ob)/Lep(ob) (ob/ob) mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH. Due to a recent ban on trans-fats as food additive, there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice. AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat. METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-Ea t (Primex shortening) substituted by equivalent amounts of palm oil [Gubra amylin NASH, (GAN) diet] for 8, 12 and 16 wk. C57BL/6J mice were fed the same diets for 28 wk. AMLN and GAN diets had similar caloric content (40% fat kcal), fructose (22%) and cholesterol (2%) level. RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance. Biopsy-confirmed steatosis, lobular inflammation, hepatocyte ballooning, fibrotic liver lesions and hepatic transcriptome changes were similar in oh/oh mice fed the GAN or AMLN diet. C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets. CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsy-confirmed NASH in ob/ob and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.
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