Animal models with minimal intervention for the translational study of metabolic syndrome-associated liver diseases

Abstract

The hepatic manifestations of metabolic syndrome (MS) include nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH). Most of NASH animal models were induced by genetic alteration or choline-deficient special diet. Although these models showed important contribution to analyze the mechanism of NAFLD/NASH, they have some weak points caused by artificial intervention. We introduce five new NASH animal models with none or minimal intervention. TSOD mice and MSG mice showed obesity, type 2 diabetes mellitus, NASH and hepatocellular carcinoma (HCC) with advancing age. High-fat, high-cholesterol diet with cholic acid and steatohepatitis-inducing high-fat diet (STHD-01) can induce severe liver fibrosis in rodents. Another model, DIAR-nSTZ mice showed HCC based on type 1 diabetes by mice standard chow. By comparing various aspects of these models as well as other NASH models in existence, pathogenesis of MS-associated liver diseases including HCC can be more clarified.