Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4904
Peer-review started: April 26, 2019
First decision: May 24, 2019
Revised: June 28, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 7, 2019
The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lepob/Lepob (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.
To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.
Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat (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.
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 ob/ob mice fed the GAN or AMLN diet. C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.
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.
Core tip: The trans-fat containing amylin liver non-alcoholic steatohepatitis (NASH) (AMLN) diet has been extensively validated in mice for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH. A recent ban on trans-fats as food additive prompted the development of a new diet with similar disease-inducing properties as the AMLN diet. Here, we introduce a trans-fat-free diet high in pal m oil (Gubra amylin NASH, GAN diet) that promotes a highly similar phenotype of biopsy-confirmed fibrotic NASH in both ob/ob and C57BL/6J mice, highlighting the suitability of GAN diet-induced obese mouse models of biopsy-confirmed NASH for the characterization of novel drug therapies for NASH.