Loss of hepatic Mboat7 leads to liver fibrosis.

Acyltransferases / deficiency Adult Aged Animals Biopsy Disease Models, Animal Disease Progression Female Genotype Haplotypes Humans Inflammation / genetics Liver Cirrhosis / genetics Male Membrane Proteins / deficiency Mice, Inbred C57BL Middle Aged Non-alcoholic Fatty Liver Disease / genetics Polymorphism, Single Nucleotide
NAFLD NASH liver fibrosis, lipidomics

Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
05 2021
Historique:
received: 07 02 2020
revised: 22 05 2020
accepted: 23 05 2020
pubmed: 28 6 2020
medline: 15 12 2021
entrez: 28 6 2020
Statut: ppublish

Résumé

The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD. Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7 Allelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7 Mboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD.

Identifiants

DOI: 10.1136/gutjnl-2020-320853 PMID: 32591434 PMC: PMC8040158
pubmed: 32591434
pii: gutjnl-2020-320853
doi: 10.1136/gutjnl-2020-320853
pmc: PMC8040158
doi:

Substances chimiques

Membrane Proteins 0
Acyltransferases EC 2.3.-
MBOAT7 protein, human EC 2.3.-
Mboat7 protein, mouse EC 2.3.1-

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

940-950

Commentaires et corrections

Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Veera Raghavan Thangapandi (VR)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Oskar Knittelfelder (O)

Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Sachsen, Germany.
ORCID: 0000-0002-1565-7238

Mario Brosch (M)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Eleonora Patsenker (E)

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Olga Vvedenskaya (O)

Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Sachsen, Germany.

Stephan Buch (S)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Sebastian Hinz (S)

Department of Visceral and Thoracic Surgery, Universitatsklinikum Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany.

Alexander Hendricks (A)

Department of Visceral and Thoracic Surgery, Universitatsklinikum Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany.
ORCID: 0000-0002-7286-9245

Marina Nati (M)

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.

Alexander Herrmann (A)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Devavrat Ravindra Rekhade (DR)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Thomas Berg (T)

Division of Hepatology, Department of Oncology, Gastroenterology, Hepatology Pulmonology, and Infectious Diseases, University Hospital Leipzig, Leipzig, Sachsen, Germany.

Madlen Matz-Soja (M)

Division of Hepatology, Department of Oncology, Gastroenterology, Hepatology Pulmonology, and Infectious Diseases, University Hospital Leipzig, Leipzig, Sachsen, Germany.
Rudolf Schönheimer- Institute of Biochemistry, University of Leipzig Faculty of Medicine, Leipzig, Germany.

Klaus Huse (K)

Leibniz Institute for Age Research Fritz-Lipmann Institute, Jena, Thüringen, Germany.

Edda Klipp (E)

Department of Theoretical Biophysics, Institute of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.

Josch K Pauling (JK)

Department of Theoretical Biophysics, Institute of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
LipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising, Bayern, Germany.

Judith Ah Wodke (JA)

Department of Theoretical Biophysics, Institute of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.

Jacobo Miranda Ackerman (J)

Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Sachsen, Germany.

Malte von Bonin (MV)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
German Cancer Consortium, Heidelberg, Baden-Württemberg, Germany.

Elmar Aigner (E)

Department of Medicine, Paracelsus Medical University Salzburg, Salzburg, Austria.

Christian Datz (C)

Department of Internal Medicine, Hospital Oberndorf, Teaching Hospital of the Paracelsus Private University of Salzburg, Obendorf, Austria.
ORCID: 0000-0001-7838-4532

Witigo von Schönfels (W)

Department of Visceral and Thoracic Surgery, Universitatsklinikum Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany.

Sophie Nehring (S)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Sebastian Zeissig (S)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Christoph Röcken (C)

Department of Pathology, University Hospital Schleswig Holstein, Kiel, Schleswig-Holstein, Germany.
ORCID: 0000-0002-6989-8002

Andreas Dahl (A)

Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.

Triantafyllos Chavakis (T)

Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Sachsen, Germany.
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.
German Center for Diabetes Research, Neuherberg, Germany.
Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.

Felix Stickel (F)

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Andrej Shevchenko (A)

Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Sachsen, Germany.
ORCID: 0000-0002-5079-1109

Clemens Schafmayer (C)

Department of General, Visceral, Vascular and Transplantation Surgery, University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany.

Jochen Hampe (J)

Department of Medicine I, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany jochen.hampe@uniklinikum-dresden.de.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität (TU) Dresden, Dresden, Germany.
ORCID: 0000-0002-2421-6127

Pallavi Subramanian (P)

Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Technische Universität (TU) Dresden, Dresden, Sachsen, Germany.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Acyltransferases › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Eucaryotes › Animaux › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytodiagnostic › Biopsie › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Phénomènes génétiques › Génotype › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Phénomènes génétiques › Génotype › Haplotypes › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Loss of hepatic Mboat7 leads to liver fibrosis.
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Loss of hepatic Mboat7 leads to liver fibrosis.