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Quantitative modeli...
Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease
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- Sen, Partho, 1983- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Govaere, Olivier (author)
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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- Sinioja, Tim, 1983- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- McGlinchey, Aidan J, 1984- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper
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- Geng, Dawei (author)
- Department of Chemistry, Örebro University, Örebro, Sweden
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- Ratziu, Vlad (author)
- Assistance Publique-Hôpitaux de Paris, hôpital Beaujon, University Paris-Diderot, Paris, France
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- Bugianesi, Elisabetta (author)
- Department of Medical Sciences, Division of Gastro-Hepatology, A.O. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
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- Schattenberg, Jörn M. (author)
- Metabolic Liver Research Programm, Department of Medicine, University Hospital Mainz, Mainz, Germany
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- Vidal-Puig, Antonio (author)
- University of Cambridge Metabolic Research Laboratories, Wellcome-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
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- Allison, Michael (author)
- Liver Unit, Department of Medicine, Cambridge Biomedical Research Centre, Cambridge University NHS Foundation Trust, UK
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- Cockell, Simon (author)
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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- Daly, Ann K. (author)
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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- Hyötyläinen, Tuulia, 1971- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik
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- Anstee, Quentin M. (author)
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Center, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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- Oresic, Matej, 1967- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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(creator_code:org_t)
- Cell Press, 2022
- 2022
- English.
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In: iScience. - : Cell Press. - 2589-0042. ; 25:9
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- Health sciences
- Metabolomics
- Omics
- Systems biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sen, Partho, 198 ...
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Govaere, Olivier
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Sinioja, Tim, 19 ...
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McGlinchey, Aida ...
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Geng, Dawei
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Ratziu, Vlad
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Bugianesi, Elisa ...
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Schattenberg, Jö ...
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Vidal-Puig, Anto ...
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Allison, Michael
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Cockell, Simon
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Daly, Ann K.
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Hyötyläinen, Tuu ...
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Anstee, Quentin ...
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Oresic, Matej, 1 ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
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iScience
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Örebro University