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Mouse model of chronic and binge ethanol feeding (the NIAAA model)

Nature Protocols volume 8, pages 627–637 (2013)Cite this article

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Abstract

Chronic alcohol consumption is a leading cause of chronic liver disease worldwide, leading to cirrhosis and hepatocellular carcinoma. Currently, the most widely used model for alcoholic liver injury is ad libitum feeding with the Lieber-DeCarli liquid diet containing ethanol for 4–6 weeks; however, this model, without the addition of a secondary insult, only induces mild steatosis, slight elevation of serum alanine transaminase (ALT) and little or no inflammation. Here we describe a simple mouse model of alcoholic liver injury by chronic ethanol feeding (10-d ad libitum oral feeding with the Lieber-DeCarli ethanol liquid diet) plus a single binge ethanol feeding. This protocol for chronic-plus-single-binge ethanol feeding synergistically induces liver injury, inflammation and fatty liver, which mimics acute-on-chronic alcoholic liver injury in patients. This feeding protocol can also be extended to chronic feeding for longer periods of time up to 8 weeks plus single or multiple binges. Chronic-binge ethanol feeding leads to high blood alcohol levels; thus, this simple model will be very useful for the study of alcoholic liver disease (ALD) and of other organs damaged by alcohol consumption.

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Figure 1: Overview of the NIAAA model procedure.
Figure 2: Cage and feeding-tube setup.
Figure 3: Oral gavage.
Figure 4: Body weight changes during the chronic-plus-binge ethanol feeding model.
Figure 5: Hepatic expression of CYP2E1 and plasma ethanol levels post ethanol feeding.
Figure 6: Comparison of liver injury induced by the chronic-plus-single-binge ethanol feeding model and other feeding models.

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Acknowledgements

We greatly appreciate all current and previous lab members for their technical support and helpful discussions. We also thank L. Chedester, A. Barnes and R. Kechrid from the Office of Laboratory Animal Science for their technical and engineering support, and for their critical reading of the manuscript. This work is supported by the intramural program of NIAAA at the NIH.

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Authors and Affiliations

  1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, Maryland, USA

    Adeline Bertola, Stephanie Mathews, Sung Hwan Ki, Hua Wang & Bin Gao

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  1. Adeline Bertola
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  2. Stephanie Mathews
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Contributions

A.B. contributed to generating the data presented, making the figures and tables and drafting the procedures; S.M. contributed to drafting the materials and generating data presented in Figure 4; S.H.K. and H.W. contributed to generating the data presented in Figure 4 and B.G. contributed to drafting and the completion of the manuscript through supervision of others.

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Correspondence to Bin Gao.

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Bertola, A., Mathews, S., Ki, S. et al. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc 8, 627–637 (2013). https://doi.org/10.1038/nprot.2013.032

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