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Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease

Lookup NU author(s): Dr Olivier GovaereORCiD, Professor Ann DalyORCiD, Professor Quentin AnsteeORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022 The Author(s)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 (PNPLA3, TM6SF2, and HSD17B13). The study demonstrates dysregulated liver metabolic pathways which may contribute to the progression of NAFLD.

Publication metadata

Author(s): Sen P, Govaere O, Sinioja T, McGlinchey A, Geng D, Ratziu V, Bugianesi E, Schattenberg JM, Vidal-Puig A, Allison M, Cockell S, Daly AK, Hyotylainen T, Anstee QM, Oresic M

Publication type: Article

Publication status: Published

Journal: iScience

Year: 2022

Volume: 25

Issue: 9

Print publication date: 16/09/2022

Online publication date: 15/08/2022

Acceptance date: 11/08/2022

Date deposited: 03/07/2023

ISSN (electronic): 2589-0042

Publisher: Elsevier Inc.


DOI: 10.1016/j.isci.2022.104949


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Funder referenceFunder name
777377European Commission
Horizon 2020 Framework Program