24-Norursodeoxycholic acid ameliorates experimental alcohol-related liver disease and activates hepatic PPARγ
© 2023 The Authors..
Background & Aims: Alcohol-related liver disease (ALD) is a global healthcare challenge with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a synthetic bile acid with anti-inflammatory properties in experimental and human cholestatic liver diseases. In the present study, we explored the efficacy of norUDCA in experimental ALD.
Methods: NorUDCA was tested in a preventive and therapeutic setting in an experimental ALD model (Lieber-DeCarli diet enriched with ethanol). Liver disease was phenotypically evaluated using histology and biochemical methods, and anti-inflammatory properties and peroxisome proliferator-activated receptor gamma activation by norUDCA were evaluated in cellular model systems.
Results: NorUDCA administration ameliorated ethanol-induced liver injury, reduced hepatocyte death, and reduced the expression of hepatic pro-inflammatory cytokines including tumour necrosis factor (Tnf), Il-1β, Il-6, and Il-10. NorUDCA shifted hepatic macrophages towards an anti-inflammatory M2 phenotype. Further, norUDCA administration altered the composition of the intestinal microbiota, specifically increasing the abundance of Roseburia, Enterobacteriaceae, and Clostridum spp. In a therapeutic model, norUDCA also ameliorated ethanol-induced liver injury. Moreover, norUDCA suppressed lipopolysaccharide-induced IL-6 expression in human peripheral blood mononuclear cells and evoked peroxisome proliferator-activated receptor gamma activation.
Conclusions: NorUDCA ameliorated experimental ALD, protected against hepatic inflammation, and affected gut microbial commensalism. NorUDCA could serve as a novel therapeutic agent in the future management of patients with ALD.
Impact and implications: Alcohol-related liver disease is a global healthcare concern with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a modified bile acid, which was proven to be effective in human cholestatic liver diseases. In the present study, we found a protective effect of norUDCA in experimental alcoholic liver disease. For patients with ALD, norUDCA could be a potential new treatment option.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
JHEP reports : innovation in hepatology - 5(2023), 11 vom: 11. Nov., Seite 100872 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grander, Christoph [VerfasserIn] |
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| Links: |
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| Themen: |
Alcoholic liver disease |
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| Anmerkungen: |
Date Revised 21.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.jhepr.2023.100872 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363113266 |
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| 100 | 1 | |a Grander, Christoph |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 24-Norursodeoxycholic acid ameliorates experimental alcohol-related liver disease and activates hepatic PPARγ |
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| 500 | |a published: Electronic-eCollection | ||
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| 520 | |a © 2023 The Authors. | ||
| 520 | |a Background & Aims: Alcohol-related liver disease (ALD) is a global healthcare challenge with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a synthetic bile acid with anti-inflammatory properties in experimental and human cholestatic liver diseases. In the present study, we explored the efficacy of norUDCA in experimental ALD | ||
| 520 | |a Methods: NorUDCA was tested in a preventive and therapeutic setting in an experimental ALD model (Lieber-DeCarli diet enriched with ethanol). Liver disease was phenotypically evaluated using histology and biochemical methods, and anti-inflammatory properties and peroxisome proliferator-activated receptor gamma activation by norUDCA were evaluated in cellular model systems | ||
| 520 | |a Results: NorUDCA administration ameliorated ethanol-induced liver injury, reduced hepatocyte death, and reduced the expression of hepatic pro-inflammatory cytokines including tumour necrosis factor (Tnf), Il-1β, Il-6, and Il-10. NorUDCA shifted hepatic macrophages towards an anti-inflammatory M2 phenotype. Further, norUDCA administration altered the composition of the intestinal microbiota, specifically increasing the abundance of Roseburia, Enterobacteriaceae, and Clostridum spp. In a therapeutic model, norUDCA also ameliorated ethanol-induced liver injury. Moreover, norUDCA suppressed lipopolysaccharide-induced IL-6 expression in human peripheral blood mononuclear cells and evoked peroxisome proliferator-activated receptor gamma activation | ||
| 520 | |a Conclusions: NorUDCA ameliorated experimental ALD, protected against hepatic inflammation, and affected gut microbial commensalism. NorUDCA could serve as a novel therapeutic agent in the future management of patients with ALD | ||
| 520 | |a Impact and implications: Alcohol-related liver disease is a global healthcare concern with limited treatment options. 24-Norursodeoxycholic acid (NorUDCA) is a modified bile acid, which was proven to be effective in human cholestatic liver diseases. In the present study, we found a protective effect of norUDCA in experimental alcoholic liver disease. For patients with ALD, norUDCA could be a potential new treatment option | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alcoholic liver disease | |
| 650 | 4 | |a M2 macrophages | |
| 650 | 4 | |a Microbiota | |
| 650 | 4 | |a Ppar-gamma | |
| 650 | 4 | |a norUDCA | |
| 700 | 1 | |a Meyer, Moritz |e verfasserin |4 aut | |
| 700 | 1 | |a Steinacher, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Claudel, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Hausmann, Bela |e verfasserin |4 aut | |
| 700 | 1 | |a Pjevac, Petra |e verfasserin |4 aut | |
| 700 | 1 | |a Grabherr, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Oberhuber, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Grander, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Brigo, Natascha |e verfasserin |4 aut | |
| 700 | 1 | |a Jukic, Almina |e verfasserin |4 aut | |
| 700 | 1 | |a Schwärzler, Julian |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Günter |e verfasserin |4 aut | |
| 700 | 1 | |a Adolph, Timon E |e verfasserin |4 aut | |
| 700 | 1 | |a Trauner, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Tilg, Herbert |e verfasserin |4 aut | |
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