Kupffer Cells pp 145-157 | Cite as

Mouse Model of Alcoholic Steatohepatitis

Part of the Methods in Molecular Biology book series (MIMB, volume 2164)


Alcoholic liver disease (ALD) is one of the most common causes of chronic liver disease in Western countries. The spectrum of ALD ranges from simple steatosis to steatohepatitis to cirrhosis and hepatocellular carcinoma. Over the past 50 years, several animal models of ALD have been developed. Although none of them faithfully recapitulates the human disease, they have proven to be invaluable tools to study the pathogenesis of ALD, to identify potential therapeutic targets and to test new drugs. Here, we describe the mouse model of chronic and binge ethanol feeding, also known as the NIAAA model or Gao binge model. This model combines chronic feeding of Lieber–DeCarli ethanol liquid diet with acute administration of high-dose ethanol by oral gavage to mimic the drinking patterns of many alcoholic patients who engage in episodes of binge drinking on top of chronic daily drinking. Short-term (10-day) chronic plus single binge ethanol feeding causes a substantial increase in serum transaminase levels, moderate steatosis and mild inflammation characterized by lobular neutrophil infiltration. Long-term (8-week) chronic plus single or multiple (twice a week) binge ethanol feeding induce more severe steatohepatitis and mild fibrosis. This clinically relevant, easy-to-perform model of ALD is currently used by many research laboratories to reproduce early stages of human alcoholic steatohepatitis.

Key words

Mouse model Alcoholic liver disease Fatty liver Steatohepatitis Fibrosis Chronic and binge ethanol feeding 


  1. 1.
    Mathurin P, Bataller R (2015) Trends in the management and burden of alcoholic liver disease. J Hepatol 62(1 Suppl):S38–S46. Scholar
  2. 2.
    Gao B, Bataller R (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141(5):1572–1585. Scholar
  3. 3.
    Mandrekar P, Bataller R, Tsukamoto H, Gao B (2016) Alcoholic hepatitis: translational approaches to develop targeted therapies. Hepatology 64(4):1343–1355. Scholar
  4. 4.
    Bertola A (2018) Rodent models of fatty liver diseases. Liver Res 2(1):1–11. Scholar
  5. 5.
    Mathews S, Xu M, Wang H, Bertola A, Gao B (2014) Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol 306(10):G819–G823. Scholar
  6. 6.
    Tsukamoto H, Machida K, Dynnyk A, Mkrtchyan H (2009) “Second hit” models of alcoholic liver disease. Semin Liver Dis 29(2):178–187. Scholar
  7. 7.
    Lazaro R, Wu R, Lee S, Zhu NL, Chen CL, French SW, Xu J, Machida K, Tsukamoto H (2014) Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice. Hepatology 61:129. Scholar
  8. 8.
    Ueno A, Lazaro R, Wang PY, Higashiyama R, Machida K, Tsukamoto H (2012) Mouse intragastric infusion (iG) model. Nat Protoc 7(4):771–781. Scholar
  9. 9.
    Bertola A, Park O, Gao B (2013) Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: a critical role for E-selectin. Hepatology 58(5):1814–1823. Scholar
  10. 10.
    Cai Y, Xu MJ, Koritzinsky EH, Zhou Z, Wang W, Cao H, Yuen PS, Ross RA, Star RA, Liangpunsakul S, Gao B (2017) Mitochondrial DNA-enriched microparticles promote acute-on-chronic alcoholic neutrophilia and hepatotoxicity. JCI Insight 2(14):e92634. Scholar
  11. 11.
    Ki SH, Park O, Zheng M, Morales-Ibanez O, Kolls JK, Bataller R, Gao B (2010) Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology 52(4):1291–1300. Scholar
  12. 12.
    Li M, He Y, Zhou Z, Ramirez T, Gao Y, Gao Y, Ross RA, Cao H, Cai Y, Xu M, Feng D, Zhang P, Liangpunsakul S, Gao B (2017) MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47(phox)-oxidative stress pathway in neutrophils. Gut 66(4):705–715. Scholar
  13. 13.
    Mathews S, Feng D, Maricic I, Ju C, Kumar V, Gao B (2016) Invariant natural killer T cells contribute to chronic-plus-binge ethanol-mediated liver injury by promoting hepatic neutrophil infiltration. Cell Mol Immunol 13(2):206–216. Scholar
  14. 14.
    Xu MJ, Cai Y, Wang H, Altamirano J, Chang B, Bertola A, Odena G, Lu J, Tanaka N, Matsusue K, Matsubara T, Mukhopadhyay P, Kimura S, Pacher P, Gonzalez FJ, Bataller R, Gao B (2015) Fat-specific protein 27/CIDEC promotes development of alcoholic steatohepatitis in mice and humans. Gastroenterology 149(4):1030–1041.e1036. Scholar
  15. 15.
    Gao B, Xu MJ, Bertola A, Wang H, Zhou Z, Liangpunsakul S (2017) Animal models of alcoholic liver disease: pathogenesis and clinical relevance. Gene Expr 17(3):173–186. Scholar
  16. 16.
    Fulham MA, Mandrekar P (2016) Sexual dimorphism in alcohol induced adipose inflammation relates to liver injury. PLoS One 11(10):e0164225. Scholar
  17. 17.
    Ramirez T, Li YM, Yin S, Xu MJ, Feng D, Zhou Z, Zang M, Mukhopadhyay P, Varga ZV, Pacher P, Gao B, Wang H (2017) Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression. J Hepatol 66(3):601–609. Scholar
  18. 18.
    Kirpich IA, Miller ME, Cave MC, Joshi-Barve S, McClain CJ (2016) Alcoholic liver disease: update on the role of dietary fat. Biomol Ther 6(1):1. Scholar
  19. 19.
    Bertola A, Mathews S, Ki SH, Wang H, Gao B (2013) Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc 8(3):627–637. Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

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