[HTML][HTML] Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source
ML Boland, D Oró, KS Tølbøl, ST Thrane… - World journal of …, 2019 - ncbi.nlm.nih.gov
ML Boland, D Oró, KS Tølbøl, ST Thrane, JC Nielsen, TS Cohen, DE Tabor, F Fernandes…
World journal of gastroenterology, 2019•ncbi.nlm.nih.govBACKGROUND 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 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 …
NASH) diet has been extensively validated in C57BL/6J 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 …
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 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-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 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.
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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