Animal models of non‐alcoholic fatty liver disease: current perspectives and recent advances

<jats:title>Abstract</jats:title><jats:p>Non‐alcoholic fatty liver disease (<jats:styled-content style="fixed-case">NAFLD</jats:styled-content>) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. <jats:styled-content style="fixed-case">NAFLD</jats:styled-content> progresses from simple liver steatosis to non‐alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (<jats:styled-content style="fixed-case">HCC</jats:styled-content>). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human <jats:styled-content style="fixed-case">NAFLD</jats:styled-content> have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of <jats:styled-content style="fixed-case">NAFLD</jats:styled-content>, the most frequently used and recently developed animal models for each stage of <jats:styled-content style="fixed-case">NAFLD</jats:styled-content> and <jats:styled-content style="fixed-case">NAFLD</jats:styled-content>‐induced <jats:styled-content style="fixed-case">HCC</jats:styled-content>, the main mechanisms involved in the experimental pathogenesis of <jats:styled-content style="fixed-case">NAFLD</jats:styled-content> in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of <jats:styled-content style="fixed-case">NAFLD</jats:styled-content> pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 2016 The Authors. <jats:italic>The Journal of Pathology</jats:italic> published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</jats:p>