Animal models of non-alcoholic steatohepatitis: of mice and man.
The epidemic occurrence of obesity has led to a rapid increase in the incidence of non-alcoholic fatty liver disease (NAFLD) in industrial countries. The disease spectrum includes hepatic steatosis, lobular inflammation with steatohepatitis (NASH) and varying degrees of liver fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma can develop in patients with NASH, even in the absence of cirrhosis. The majority of patients with primary NASH exhibit risk factors that define the metabolic syndrome including insulin resistance and visceral obesity. However, only a minority of patients with NAFLD progress to end-stage liver disease and, so far, predictors to identify these patients are not available. The course of disease progression appears to be slow and develops progressively over years, modulated by genetic susceptibility, nutritional misbehavior and environmental factors. Although risk factors have been identified in epidemiological studies, little is known about disease initiation and progression. This review summarizes the existing animal models of NAFLD, focusing on genetic and dietary models, and discusses their applicability in studying signaling events involved in steatohepatitis. Despite the shortcomings inherent to all experimental models, research in this field has helped to identify potential therapeutic targets and, thus, contributed significantly to our understanding of this disease. The validation and search for new in vivo and in vitro models will propagate the understanding of NASH and help clinicians to develop new treatment modalities.
Schattenberg
J M
JM
I. Medizinische Klinik, Universitätsmedizin der Johannes Gutenberg-Universität, Mainz, Germany. schatten@uni-mainz.de
Galle
P R
PR
D000818:Animals; D002796:Choline Deficiency / Q000150:complications; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000473:pathology; D008715:Methionine / Q000172:deficiency; D051379:Mice
D004041:Dietary Fats; D008715:Methionine