دورية أكاديمية
أعرض في EDS

Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF.

التفاصيل البيبلوغرافية
العنوان: Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF.
المؤلفون: Moreau R; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI) UMRS1149, Université de Paris, Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. Electronic address: richard.moreau@inserm.fr., Clària J; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain; CIBERehd, Barcelona, Spain., Aguilar F; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain., Fenaille F; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Lozano JJ; CIBERehd, Barcelona, Spain., Junot C; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Colsch B; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Caraceni P; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Trebicka J; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; J.W. Goethe University Hospital, Frankfurt, Germany., Pavesi M; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain., Alessandria C; Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy., Nevens F; University Hospital Gasthuisberg, KU Leuven, Belgium., Saliba F; Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France., Welzel TM; J.W. Goethe University Hospital, Frankfurt, Germany., Albillos A; Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain., Gustot T; CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium., Fernández J; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain; CIBERehd, Barcelona, Spain., Moreno C; CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium., Baldassarre M; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Zaccherini G; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Piano S; Unit of Internal Medicine and Hepatology, Dept. of Medicine, DIMED, University of Padova, Italy., Montagnese S; Unit of Internal Medicine and Hepatology, Dept. of Medicine, DIMED, University of Padova, Italy., Vargas V; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain., Genescà J; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain., Solà E; Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain; CIBERehd, Barcelona, Spain., Bernal W; Liver Intensive Therapy Unit, Institute of Liver Studies, Division of Inflammation Biology, King's College London, London, UK., Butin N; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Hautbergue T; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Cholet S; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Castelli F; Service de Pharmacologie et Immuno-Analyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments, CEA, INRA, Université Paris Saclay, MetaboHUB, F-91191 Gif-sur-Yvette, France., Jansen C; Department of Internal Medicine I, University of Bonn, Germany., Steib C; Department of Medicine II, Liver Center Munich, University Hospital LMU Munich, Munich, Germany., Campion D; Division of Gastroenterology and Hepatology, San Giovanni Battista Hospital, Torino, Italy., Mookerjee R; Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, UK., Rodríguez-Gandía M; Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain., Soriano G; Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain., Durand F; Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI) UMRS1149, Université de Paris, Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France., Benten D; University Hospital Hamburg-Eppendorf, Germany., Bañares R; Digestive Diseases Department, Hospital General Universitario Gregorio Marañón; Instituto de Investigación Sanitaria Gregorio Marañón; Facultad de Medicina, Universidad Complutense, Madrid; and CIBERehd., Stauber RE; Medical University of Graz, Graz, Austria., Gronbaek H; Department of Hepatology & Gastroenterology, Aarhus University Hospital, Aarhus, Denmark., Coenraad MJ; Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands., Ginès P; Hospital Clínic-IDIBAPS, Universitat de Barcelona, Barcelona, Spain; CIBERehd, Barcelona, Spain., Gerbes A; Department of Medicine II, Liver Center Munich, University Hospital LMU Munich, Munich, Germany., Jalan R; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, UK., Bernardi M; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Arroyo V; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain., Angeli P; EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain; Unit of Internal Medicine and Hepatology, Dept. of Medicine, DIMED, University of Padova, Italy.
مؤلفون مشاركون: CANONIC Study Investigators of the EASL Clif Consortium, Grifols Chair, European Foundation for the Study of Chronic Liver Failure (EF Clif)
المصدر: Journal of hepatology [J Hepatol] 2020 Apr; Vol. 72 (4), pp. 688-701. Date of Electronic Publication: 2019 Nov 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8503886 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0641 (Electronic) Linking ISSN: 01688278 NLM ISO Abbreviation: J Hepatol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2001- : Amsterdam : Elsevier
Original Publication: Copehnagen : Munksgaard International Publishers, [c1984-
مواضيع طبية MeSH: Glycolysis* , Metabolome*, Acute-On-Chronic Liver Failure/*blood , Acute-On-Chronic Liver Failure/*complications , Liver Cirrhosis/*blood , Liver Cirrhosis/*complications , Metabolomics/*methods , Mitochondria/*metabolism, Adult ; Aged ; Biomarkers/blood ; Case-Control Studies ; Female ; Humans ; Inflammation/metabolism ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index
مستخلص: Background & Aims: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF.
Methods: We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy individuals.
Results: Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 comprised a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher the plasma levels of inflammatory markers, tumor necrosis factor α, soluble CD206, and soluble CD163. ACLF was characterized by intense proteolysis and lipolysis; amino acid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid β-oxidation; and extra-mitochondrial amino acid metabolism giving rise to metabotoxins.
Conclusions: In ACLF, intense systemic inflammation is associated with blood metabolite accumulation and profound alterations in major metabolic pathways, in particular inhibition of mitochondrial energy production, which may contribute to the development of organ failures.
Lay Summary: Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. We identified a 38-metabolite blood fingerprint specific for ACLF that revealed mitochondrial dysfunction in peripheral organs. This may contribute to organ failures.
(Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
التعليقات: Erratum in: J Hepatol. 2020 Jun;72(6):1218-1220. (PMID: 32192825)
Comment in: J Hepatol. 2020 Sep;73(3):732-734. (PMID: 32653223)
Comment in: J Hepatol. 2020 Sep;73(3):730-732. (PMID: 32674883)
Comment in: J Hepatol. 2022 Sep;77(3):874-876. (PMID: 35562066)
فهرسة مساهمة: Keywords: Biomarkers; CANONIC study; Multiorgan failure, Small-molecules
المشرفين على المادة: 0 (Biomarkers)
تواريخ الأحداث: Date Created: 20191129 Date Completed: 20211006 Latest Revision: 20221005
رمز التحديث: 20240829
DOI: 10.1016/j.jhep.2019.11.009
PMID: 31778751
قاعدة البيانات: MEDLINE
الوصف
تدمد:1600-0641
DOI:10.1016/j.jhep.2019.11.009