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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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2014 (Engelska)Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, s. 3083-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
2014. Vol. 5, s. 3083-
Nyckelord [en]
Hepatocellular-Carcinoma, Global Reconstruction, Gene-Expression, Network, Steatohepatitis, Steatosis, Methionine, Prediction, Biomarkers, Physiology
Nationell ämneskategori
Medicin och hälsovetenskap Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:kth:diva-143466DOI: 10.1038/ncomms4083ISI: 000331084200025OAI: oai:DiVA.org:kth-143466DiVA, id: diva2:707584
Forskningsfinansiär
Knut och Alice Wallenbergs StiftelseScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Anmärkning

QC 20140325

Tillgänglig från: 2014-03-25 Skapad: 2014-03-21 Senast uppdaterad: 2020-01-10Bibliografiskt granskad

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Uhlén, Mathias

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Uhlén, MathiasNielsen, Jens
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Proteomik och nanobioteknologiScience for Life Laboratory, SciLifeLabGenteknologi
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Nature Communications
Medicin och hälsovetenskapBiologiska vetenskaper

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