Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation

Bile acid; Inflammation; Oncostatin M

Bibliographic Details
Authors: Alonso-Peña, Marta, Espinosa-Escudero, Ricardo A., Hermanns, Heike, Briz Sanchez, Oscar, Garcia-Ruiz, Carmen, Juamperez Goñi, Javier, Herranz Alzueta, Jose Mari
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/8872
Online Access:https://hdl.handle.net/11351/8872
Access Level:Open access
Keyword:Fetge - Malalties
Inflamació
Àcids biliars
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
DISEASES::Digestive System Diseases::Liver Diseases
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas
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oai_identifier_str oai:recercat.cat:11351/8872
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
title Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
spellingShingle Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
Alonso-Peña, Marta
Fetge - Malalties
Inflamació
Àcids biliars
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
DISEASES::Digestive System Diseases::Liver Diseases
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas
title_short Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
title_full Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
title_fullStr Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
title_full_unstemmed Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
title_sort Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation
dc.creator.none.fl_str_mv Alonso-Peña, Marta
Espinosa-Escudero, Ricardo A.
Hermanns, Heike
Briz Sanchez, Oscar
Garcia-Ruiz, Carmen
Juamperez Goñi, Javier
Herranz Alzueta, Jose Mari
author Alonso-Peña, Marta
author_facet Alonso-Peña, Marta
Espinosa-Escudero, Ricardo A.
Hermanns, Heike
Briz Sanchez, Oscar
Garcia-Ruiz, Carmen
Juamperez Goñi, Javier
Herranz Alzueta, Jose Mari
author_role author
author2 Espinosa-Escudero, Ricardo A.
Hermanns, Heike
Briz Sanchez, Oscar
Garcia-Ruiz, Carmen
Juamperez Goñi, Javier
Herranz Alzueta, Jose Mari
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Alonso-Peña M] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain. Division of Hepatology, Würzburg University Hospital, Medical Clinic II, Würzburg, Germany. [Espinosa-Escudero R] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. [Hermanns HM] Division of Hepatology, Würzburg University Hospital, Medical Clinic II, Würzburg, Germany. [Briz O] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. [Herranz JM] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. Hepatology Program, Liver Unit, Instituto de Investigación de Navarra (IdisNA), Clínica Universidad de Navarra and Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain. [Garcia-Ruiz C] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. Institute of Biomedical Research of Barcelona (IIBB), Centro Superior de Investigaciones Científicas (CSIC), Barcelona, Spain. Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Juamperez J] Unitat de Gastroenterologia, Hepatologia, Suport Nutricional i Trasplantaments Hepàtics Pediàtrics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Fetge - Malalties
Inflamació
Àcids biliars
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
DISEASES::Digestive System Diseases::Liver Diseases
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas
topic Fetge - Malalties
Inflamació
Àcids biliars
CHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and Salts
DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
DISEASES::Digestive System Diseases::Liver Diseases
COMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliares
ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamación
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas
description Bile acid; Inflammation; Oncostatin M
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/8872
url https://hdl.handle.net/11351/8872
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cells;11(24)
https://doi.org/10.3390/cells11243983
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420079581495297
spelling Impact of Liver Inflammation on Bile Acid Side Chain Shortening and AmidationAlonso-Peña, MartaEspinosa-Escudero, Ricardo A.Hermanns, HeikeBriz Sanchez, OscarGarcia-Ruiz, CarmenJuamperez Goñi, JavierHerranz Alzueta, Jose MariFetge - MalaltiesInflamacióÀcids biliarsCHEMICALS AND DRUGS::Polycyclic Compounds::Fused-Ring Compounds::Steroids::Bile Acids and SaltsDISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationDISEASES::Digestive System Diseases::Liver DiseasesCOMPUESTOS QUÍMICOS Y DROGAS::compuestos policíclicos::compuestos con anillos de fusión::esteroides::ácidos y sales biliaresENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::inflamaciónENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticasBile acid; Inflammation; Oncostatin MÀcid biliar; Inflamació; Oncostatina MÁcido biliar; Inflamación; Oncostatina MBile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4α (HNF4α) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7α-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4α levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.This study was supported by the CIBERehd (EHD15PI05/2016) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819, PI20/00189, and PI20/01663 co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Junta de Castilla y Leon (SA074P20); Fundació Marato TV3 (Ref. 201916/31), Spain; AECC Scientific Foundation (2017/2020), Spain; Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of Wuerzburg, Germany (Project A-E-384 to H.M.H.); grants PID2019-111669-RB-I00, PID2020-115055RB-I00 from Agencia Estatal de Investigación (AEI), Spain; the AGAUR of the Generalidad de Cataluña SGR-2017-1112, Spain; and European Cooperation in Science & Technology (COST) Action CA17112. R.E.E was recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). J.A. was recipient of a grant from Fundación Echebano (2020–2022).MDPIInstitut Català de la Salut[Alonso-Peña M] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain. Division of Hepatology, Würzburg University Hospital, Medical Clinic II, Würzburg, Germany. [Espinosa-Escudero R] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. [Hermanns HM] Division of Hepatology, Würzburg University Hospital, Medical Clinic II, Würzburg, Germany. [Briz O] Experimental Hepatology and Drug Targeting (HEVEPHARM), Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. [Herranz JM] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. Hepatology Program, Liver Unit, Instituto de Investigación de Navarra (IdisNA), Clínica Universidad de Navarra and Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain. [Garcia-Ruiz C] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Institute of Health, Madrid, Spain. Institute of Biomedical Research of Barcelona (IIBB), Centro Superior de Investigaciones Científicas (CSIC), Barcelona, Spain. Center for ALPD, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Juamperez J] Unitat de Gastroenterologia, Hepatologia, Suport Nutricional i Trasplantaments Hepàtics Pediàtrics, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, SpainVall d'Hebron Barcelona Hospital Campus202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8872Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCells;11(24)https://doi.org/10.3390/cells11243983Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/88722026-05-29T05:05:01Z
score 15.811543

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