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Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease
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- Mardinoglu, Adil, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ågren, Rasmus, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kampf, Caroline (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab
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- (creator_code:org_t)
- 2014-01-14
- 2014
- English.
- In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3083-
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Keyword
- Hepatocellular-Carcinoma
- Global Reconstruction
- Gene-Expression
- Network
- Steatohepatitis
- Steatosis
- Methionine
- Prediction
- Biomarkers
- Physiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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