Z Gastroenterol 2023; 61(05): e196
DOI: 10.1055/s-0043-1769052
Abstracts | ÖGGH
POSTER
Hepatologie

24-norursodeoxycholic acid ameliorates experimental alcoholic liver disease and activates hepatic peroxisome proliferator-activated receptor gamma

Authors

  • C. Grander

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • M. Meyer

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • D. Steinacher

    2   Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

  • T. Claudel

    2   Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

  • M. Grander

    3   Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria

  • B. Hausmann

    4   Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria

  • P. Pjevac

    4   Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria

  • B. Enrich

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • F. Grabherr

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • G. Oberhuber

    5   INNPATH, Tirol-Kliniken University Hospital Innsbruck, Innsbruck, Austria.

  • A. Jukic

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • J. Schwärzler

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • T. E. Adolph

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria

  • G. Weiss

    3   Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Innsbruck, Austria

  • M. Trauner

    2   Hans Popper Laboratory of Molecular Hepatology, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

  • H. Tilg

    1   Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria
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Background  The limited treatment options in alcoholic liver disease (ALD) remain one of the major healthcare problems worldwide. For example, alcohol associated cirrhosis-related deaths are rising globally and ALD is still the main driver of liver transplantation in Europe. In this project, we explored if the synthetic bile acid 24-norursodeoxycholic acid (norUDCA) could serve as novel therapeutic in experimental ALD.

Materials and methods  Wildtype mice were fed an ethanol containing Lieber-DeCarli diet for 15 days. In a preventive model, norUDCA was administered starting from day one while in a therapeutic setting, norUDCA was supplemented from day 10 on.

We assessed liver disease by histology as well as biochemical methods including qPCR, immunohistochemistry and Western Blot while the anti-inflammatory properties and the activation of peroxisome proliferator-activated receptor gamma (PPARγ) were evaluated using an in vitro cell culture system.

Results  Preventive norUDCA treatment alleviated ethanol-induced liver injury and led to a significant reduction in serum ALT and hepatic steatosis as well as hepatocyte apoptosis. We could demonstrate that norUDCA administration reduced the transcription of pro-inflammatory cytokines such as Tnf, Il1b, Il10 and Il6 while hepatic PPARγ protein expression was increased. Moreover, the administration of norUDCA was associated with an increase in anti-inflammatory M2-polarized hepatic macrophages. We could further show that the administration of norUDCA blunted LPS induced IL-6 production of human PBMC and the enhancement of nuclear PPARγ by norUDCA was confirmed in norUDCA treated immortalized human hepatocytes.

Furthermore, five days of therapeutic norUDCA treatment after already established ALD was effective in reducing alcohol induced hepatic Tnf, Il10 and Il6 expression and led to a significant increase in hepatic Pparg.

Conclusions  In an experimental model of ALD, norUDCA was effective in reducing hepatic inflammation, potentially by increasing hepatic PPARγ. Further clinical studies are now warranted to prove its effect in human ALD.


Publication History

Article published online:
24 May 2023

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