Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source.
World J Gastroenterol
; 25(33): 4904-4920, 2019 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-31543682
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 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.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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Óleo de Palmeira
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Modelos Animais de Doenças
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Hepatopatia Gordurosa não Alcoólica
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Fígado
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos