Change search
ReferencesLink to record
Permanent link

Direct link
Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease
Show others and affiliations
2014 (English)In: Nature Communications, ISSN 2041-1723, Vol. 5, 3083- p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2014. Vol. 5, 3083- p.
Keyword [en]
Hepatocellular-Carcinoma, Global Reconstruction, Gene-Expression, Network, Steatohepatitis, Steatosis, Methionine, Prediction, Biomarkers, Physiology
National Category
Medical and Health Sciences Biological Sciences
URN: urn:nbn:se:kth:diva-143466DOI: 10.1038/ncomms4083ISI: 000331084200025OAI: diva2:707584
Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience

QC 20140325

Available from: 2014-03-25 Created: 2014-03-21 Last updated: 2014-03-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Uhlén, MathiasNielsen, Jens
By organisation
Proteomics and NanobiotechnologyScience for Life Laboratory, SciLifeLabGene Technology
In the same journal
Nature Communications
Medical and Health SciencesBiological Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 200 hits
ReferencesLink to record
Permanent link

Direct link