Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease
2014 (English)In: Nature Communications, ISSN 2041-1723, Vol. 5, 3083- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 5, 3083- p.
Hepatocellular-Carcinoma, Global Reconstruction, Gene-Expression, Network, Steatohepatitis, Steatosis, Methionine, Prediction, Biomarkers, Physiology
Medical and Health Sciences Biological Sciences
IdentifiersURN: urn:nbn:se:kth:diva-143466DOI: 10.1038/ncomms4083ISI: 000331084200025OAI: oai:DiVA.org:kth-143466DiVA: diva2:707584
FunderKnut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 201403252014-03-252014-03-212014-03-25Bibliographically approved