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Curr Protoc Mouse Biol. 2016 Jun 1;6(2):201-10. doi: 10.1002/cpmo.1.

Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

Author information

1
Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
2
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
3
Department of Laboratory Medicine, University Hospitals KU Leuven, Leuven, Belgium.
4
Metabolic Center, University Hospitals KU Leuven, Leuven, Belgium.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH.

KEYWORDS:

NAFLD; NASH; fibrosis; fructose; mouse model; sucrose

PMID:
27248435
DOI:
10.1002/cpmo.1
[Indexed for MEDLINE]

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