title: Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.
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. © 2016 by John Wiley & Sons, Inc.
authors.affiliation: Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.|Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Jef
authors.initials: J
authors.lastname: Verbeek
authors.affiliation: Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
authors.forename: Ans
authors.initials: A
authors.lastname: Jacobs
authors.affiliation: Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.|Department of Laboratory Medicine, University Hospitals KU Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Spincemaille
authors.affiliation: Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.|Metabolic Center, University Hospitals KU Leuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
mesh_terms: D000818:Animals; D000070601:Diet, Carbohydrate Loading; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology*
keywords: NAFLD; NASH; fibrosis; fructose; mouse model; sucrose