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Animal models of nonalcoholic fatty liver disease

Nature Reviews Gastroenterology & Hepatology volume 8, pages 35–44 (2011)Cite this article

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Abstract

In 1980, Ludwig and colleagues described a series of patients with liver histology characterized by the accumulation of fat and the presence of hepatic necroinflammation in the absence of a history of excessive alcohol consumption. They coined the term nonalcoholic steatohepatitis (NASH), which today is regarded as one of the most common causes of liver disease in affluent countries. NASH is a subset of a larger spectrum of diseases termed fatty liver disease (including alcoholic and nonalcoholic fatty liver disease; AFLD and NAFLD, respectively). NAFLD and NASH are linked to visceral adiposity, insulin resistance, dyslipidemia and type 2 diabetes, and are increasing due to the prevalence of the metabolic syndrome. In this context, research has been undertaken using animals to model human steatosis and NAFLD to NASH disease progression. This Review discusses the prevalent dietary and inflammation-based genetic animal models described in recent years.

Key Points

  • Hepatic steatosis is associated with the metabolic syndrome

  • No dietary animal model can fully recapitulate the human steatosis disease process

  • Genetic models have shown adipose inflammation to drive hepatic steatosis

  • Cholesterol promotes hepatic inflammation

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Figure 1: Histopathologic specimens of human liver.
Figure 2: The 'integrated response' hypothesis of nonalcoholic fatty liver disease pathogenesis: current concepts of tissue crosstalk that can promote hepatic steatosis and inflammation.
Figure 3: Obesity promotes adipocyte inflammation and steatosis.
Figure 4: Cholesterol can promote steatosis.

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Acknowledgements

L. Hebbard and J. George are supported by a Project Grant from the National Health and Medical Research Council, Australia (No: 632630) and the Robert W. Storr Bequest to the Medical Foundation of the University of Sydney.

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  1. Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Darcy Road, Westmead, 2145, NSW, Australia

    Lionel Hebbard & Jacob George

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L. Hebbard and J. George contributed equally to the research, discussion, writing and reviewing of the manuscript.

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Hebbard, L., George, J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 8, 35–44 (2011). https://doi.org/10.1038/nrgastro.2010.191

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