Skip to main content
SpringerLink
Log in

Mouse Model of Alcoholic Steatohepatitis

  • Protocol
  • First Online:
Kupffer Cells

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

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Mathurin P, Bataller R (2015) Trends in the management and burden of alcoholic liver disease. J Hepatol 62(1 Suppl):S38–S46. https://doi.org/10.1016/j.jhep.2015.03.006

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gao B, Bataller R (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141(5):1572–1585. https://doi.org/10.1053/j.gastro.2011.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mandrekar P, Bataller R, Tsukamoto H, Gao B (2016) Alcoholic hepatitis: translational approaches to develop targeted therapies. Hepatology 64(4):1343–1355. https://doi.org/10.1002/hep.28530

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bertola A (2018) Rodent models of fatty liver diseases. Liver Res 2(1):1–11. https://doi.org/10.1016/j.livres.2018.03.001

    Article  Google Scholar 

  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. https://doi.org/10.1152/ajpgi.00041.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tsukamoto H, Machida K, Dynnyk A, Mkrtchyan H (2009) “Second hit” models of alcoholic liver disease. Semin Liver Dis 29(2):178–187. https://doi.org/10.1055/s-0029-1214373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1002/hep.27383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1038/nprot.2012.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1002/hep.26419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1172/jci.insight.92634

    Article  PubMed Central  Google Scholar 

  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. https://doi.org/10.1002/hep.23837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1136/gutjnl-2016-311861

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1038/cmi.2015.06

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1053/j.gastro.2015.06.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.3727/105221617X695519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Fulham MA, Mandrekar P (2016) Sexual dimorphism in alcohol induced adipose inflammation relates to liver injury. PLoS One 11(10):e0164225. https://doi.org/10.1371/journal.pone.0164225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1016/j.jhep.2016.11.004

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3390/biom6010001

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1038/nprot.2013.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Adeline Bertola

Authors
  1. Adeline Bertola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adeline Bertola .

Editor information

Editors and Affiliations

  1. Department of Medicine, Integrated Cardio Metabolic Center, Karolinska Institutet, Huddinge, Sweden

    Myriam Aouadi

  2. Department of Medicine, Integrated Cardio Metabolic Center, Karolinska Institutet, Huddinge, Sweden

    Valerio Azzimato

Rights and permissions

Reprints and permissions

Copyright information

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

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Bertola, A. (2020). Mouse Model of Alcoholic Steatohepatitis. In: Aouadi, M., Azzimato, V. (eds) Kupffer Cells. Methods in Molecular Biology, vol 2164. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0704-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0704-6_15

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0703-9

  • Online ISBN: 978-1-0716-0704-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation