التفاصيل البيبلوغرافية
| العنوان: |
Quantitative modeling of human liver reveals dysregulation of glycosphingolipid pathways in nonalcoholic fatty liver disease |
| المؤلفون: |
Partho Sen, Olivier Govaere, Tim Sinioja, Aidan McGlinchey, Dawei Geng, Vlad Ratziu, Elisabetta Bugianesi, Jörn M. Schattenberg, Antonio Vidal-Puig, Michael Allison, Simon Cockell, Ann K. Daly, Tuulia Hyötyläinen, Quentin M. Anstee, Matej Orešič |
| المصدر: |
iScience, Vol 25, Iss 9, Pp 104949- (2022) |
| بيانات النشر: |
Elsevier, 2022. |
| سنة النشر: |
2022 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
Health sciences, Systems biology, Omics, Metabolomics, Science |
| الوصف: |
Summary: 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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2589-0042 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2589004222012214; https://doaj.org/toc/2589-0042 |
| DOI: |
10.1016/j.isci.2022.104949 |
| URL الوصول: |
https://doaj.org/article/ff48a05fd4c04ac5b4dbc6cdda589a9f |
| رقم الانضمام: |
edsdoj.ff48a05fd4c04ac5b4dbc6cdda589a9f |
| قاعدة البيانات: |
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