Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease.
Health sciences
Metabolomics
Omics
Systems biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
16 Sep 2022
16 Sep 2022
Historique:
received:
10
09
2021
revised:
21
01
2022
accepted:
11
08
2022
entrez:
6
9
2022
pubmed:
7
9
2022
medline:
7
9
2022
Statut:
epublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease that is associated with multiple metabolic disturbances, yet the metabolic pathways underlying its progression are poorly understood. Here, we studied metabolic pathways of the human liver across the full histological spectrum of NAFLD. We analyzed whole liver tissue transcriptomics and serum metabolomics data obtained from a large, prospectively enrolled cohort of 206 histologically characterized patients derived from the European NAFLD Registry and developed genome-scale metabolic models (GEMs) of human hepatocytes at different stages of NAFLD. We identified several metabolic signatures in the liver and blood of these patients, specifically highlighting the alteration of vitamins (A, E) and glycosphingolipids, and their link with complex glycosaminoglycans in advanced fibrosis. Furthermore, we derived GEMs and identified metabolic signatures of three common NAFLD-associated gene variants
Identifiants
pubmed: 36065182
doi: 10.1016/j.isci.2022.104949
pii: S2589-0042(22)01221-4
pmc: PMC9440293
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104949Subventions
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0802051
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400192
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/7/33636
Pays : United Kingdom
Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
J.M.S. declares Consultancy: Boehringer Ingelheim, BMS, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Novo Nordisk, Nordic Bioscience, Pfizer, Roche, Sanofi, Siemens Healthcare GmbH. Research Funding: Gilead Sciences, Boehringer Ingelheim. Speakers Bureau: Falk Foundation MSD Sharp & Dohme GmbH. M.A. reports consultancy/advisory with MedImmune/Astra Zeneca and E3Bio, as well as honoraria from Intercept and grant support from GSK and Takeda. E.B. reports advisory/consulting for BMS, Genfit SA, Gilead, Intercept, and Novartis. Q.M.A. reports grants, personal fees and other from Allergan/Tobira, other from E3Bio, other from Eli Lilly & Company Ltd, other from Galmed, grants, personal fees and other from Genfit SA, personal fees and other from Gilead, other from Grunthal, other from Imperial Innovations, grants and other from Intercept Pharma Europe Ltd, other from Inventiva, other from Janssen, personal fees from Kenes, other from MedImmune, other from NewGene, grants, personal fees and other from Pfizer Ltd, other from Raptor Pharma, grants and other from Novartis Pharma AG, grants from Abbvie, personal fees and other from BMS, grants from GSK, other from NGMBio, other from Madrigal, other from Servier, other from EcoR1, other from 89Bio, other from Altimmune, grants and other from AstraZeneca, other from Axcella, other from Blade, other from BNN Cardio, other from Celgene, other from Cirius, other from CymaBay, other from Genentech, other from HistoIndex, other from Indalo, other from IQVIA, other from Metacrine, other from North Sea Therapeutics, personal fees and other from Novo Nordisk, other from Poxel, other from Terns, other from Viking Therapeutics, grants from Glympse Bio, other from PathAI, outside the submitted work. All other authors declare that they have no competing interests.
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