Towards a Standard Diet-induced and Biopsy-confirmed Mouse Model of Non-alcoholic Steatohepatitis: Impact of Dietary Fat Source

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2019 Sep 24

PMID 31543682

Citations 63

Authors

Michelle L Boland

Denise Oro

Kirstine S Tolbol

Sebastian T Thrane

Jens Christian Nielsen

Taylor S Cohen

David E Tabor

Fiona Fernandes

Andrey Tovchigrechko

Sanne S Veidal

Paul Warrener

Bret R Sellman

Jacob Jelsing

Michael Feigh

Niels Vrang

James L Trevaskis

Henrik H Hansen

Affiliations

Soon will be listed here.

Abstract

Background: The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lep/Lep () 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 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 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.

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 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 and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

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