Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease

• DOI: 10.1371/journal.pone.0127991
• Publication Date: 2015-05-27T17:57:16Z
• Authors: Mariana Verdelho ...; Gregory Alexander...; Guanhua Xie; Thiago Pereira de...; Jerome Boursier; Brittany Bohnic; Cynthia D. Guy; Anna Mae Diehl
• Keywords: Steatohepatitis; Steatosis

Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is pandemic our time. Although there are several animal models NASH, consensus regarding optimal model lacking. We aimed to compare features NASH in two most widely-used mouse models: methionine-choline deficient (MCD) diet Western diet. Methods Mice were fed standard chow, MCD for 8 weeks, or (45% energy from fat, predominantly saturated with 0.2% cholesterol, plus drinking water supplemented fructose glucose) 16 weeks. Liver pathology metabolic profile compared. Results The associated human was better mimicked by hepatic steatosis (i.e., triglyceride accumulation) also more severe, non-esterified acid content lower than group. less severe reproducible model, as evidenced cell death/apoptosis, inflammation, ductular reaction, fibrosis. Various mechanisms implicated pathogenesis/progression robust including oxidative stress, ER autophagy deregulation, hedgehog pathway activation. Conclusion Feeding mice a perturbations that common humans mild whereas administration pathobiological cause NAFLD progress advanced NASH.