Z Gastroenterol 2025; 63(08): e451-e452
DOI: 10.1055/s-0045-1810768
Abstracts | DGVS/DGAV
Kurzvorträge
ACLF: Klinische Realiät und experimentelle Horizonte Donnerstag, 18. September 2025, 09:30 – 10:58, Vortragsraum 10

Hepatocyte Mboat7 is a driver of inflammation and fibrosis in alcohol-associated liver disease

V R Thangapandi
1   Center for Regenerative Therapies Dresden, Dresden, Deutschland
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
,
P Subramanian
3   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Deutschland
,
M Brosch
1   Center for Regenerative Therapies Dresden, Dresden, Deutschland
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
,
L Rupp
4   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute of Immunology, Dresdende, Deutschland
,
E Patsenker
5   University Hospital of Zurich, Switzerland, Zurich, Schweiz
,
R Pérez Mateo
1   Center for Regenerative Therapies Dresden, Dresden, Deutschland
,
J Mueller
6   University of Heidelberg, Center for Alcohol Research, Heidelberg, Deutschland
,
A Herrmann
1   Center for Regenerative Therapies Dresden, Dresden, Deutschland
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
,
D Giannakou
3   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Deutschland
,
R Machangada Ganesh
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
,
S Buch
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
,
A Dahl
7   DRESDEN-concept Genome Center, TU Dresden, Dresden, Deutschland
,
V Ismini Alexaki
3   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Deutschland
,
M Fedorova
8   Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Deutschland
,
T Chavakis
3   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Deutschland
,
C Schafmayer
9   Department of General, Visceral, Vascular and Transplantation Surgery, University of Rostock, Rostock, Deutschland
,
F Stickel
5   University Hospital of Zurich, Switzerland, Zurich, Schweiz
,
E Trépo
10   Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium, Brussels, Belgien
,
S Mueller
6   University of Heidelberg, Center for Alcohol Research, Heidelberg, Deutschland
,
M Schmitz
4   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Institute of Immunology, Dresdende, Deutschland
,
J Hampe
1   Center for Regenerative Therapies Dresden, Dresden, Deutschland
2   Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Department of Gastroenterology and Hepatology, Dresden, Deutschland
› Author Affiliations
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    Background: Alcohol related liver disease (ALD) remains the dominant driver of liver mortality in world. Treatment options for ALD remains limited and MBOAT7 locus, associated with alcohol related liver cirrhosis (AC), could be a starting point for uncovering novel disease mechanisms.

    Objective: Membrane-bound-O-acyltransferase domain 7 (MBOAT7) is a transmembrane protein involved in acyl chain remodeling of phosphatidylinositol (PI) within Land’s cycle. In addition to liver disease such as metabolic dysfunction-associated steatotic liver disease (MASLD), the MBOAT7 risk variant rs641738C>T is associated with AC. This study investigates the role of hepatocyte-specific MBOAT7 in the progression of ALD.

    Design: Hepatocyte-specific MBOAT7 deficient (Mboat7Δhep) and sufficient (Mboat7WT) mice were fed an ethanol diet (modified NIAAA model) or control diet. Livers were studied by immunofluorescence, flow cytometry, histology, qPCR, RNA sequencing, lipidomic and metabolomic analyses. Metabolomic profiling was also conducted on liver biopsies from ALD patients, stratified by rs641738C>T genotype.

    Results: Ethanol diet fed, Mboat7Δhep mice developed enhanced steatosis with increased levels of cholesterol esters and triglycerides, compared to the Mboat7WT mice. Mboat7 deficiency resulted in severe inflammation, and fibrosis confirmed by histological, transcriptomic, and flow cytometry analyses. Notably, arachidonic acid-derived eicosanoids, including 5-HETE and 20-HETE, were significantly elevated in livers of ethanol-fed Mboat7Δhep mice and ALD patients with the rs641738 C>T risk variant. Treatment of ethanol-fed Mboat7Δhep mice with a 20-HETE inhibitor reduced hepatic accumulation of monocytes and macrophages, and reduced inflammatory markers such as Vcam1, Ccr2, IL1rn, and Cxcl10 (P<0.05) mitigating inflammation. This decreased inflammation corroborated with decreased fibrosis markers, particularly Col1a1, Col3a1 and Col4a2 (P<0.05).

    Conclusion: Hepatocyte-specific MBOAT7 deficiency promotes inflammation and fibrosis in ALD via arachidonic acid-derived eicosanoids, highlighting potential therapeutic targets for managing this disease.


     

    Publication History

    Article published online:
    04 September 2025

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