Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease

Mardinoglu, Adil,1982Chalmers tekniska högskola,Chalmers University of Technology (author)

QC 20140325
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.

Ågren, Rasmus,1982Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)arasmus (author)
Kampf, CarolineUppsala universitet,Molekylär och morfologisk patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)carokamp (author)
Asplund, AnnaUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär och morfologisk patologi(Swepub:uu)annaaspl (author)
Uhlén, MathiasKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)(Swepub:kth)u1dulvmw (author)
Nielsen, JensKTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (author)
Chalmers tekniska högskolaMolekylär och morfologisk patologi (creator_code:org_t)

In:Nature Communications: Springer Science and Business Media LLC5, s. 3083-2041-1723

By the author/editor: Mardinoglu, Adil ...; Ågren, Rasmus, 1 ...; Kampf, Caroline; Asplund, Anna; Uhlén, Mathias; Nielsen, Jens

About the subject

By the university: Royal Institute of Technology; Chalmers University of Technology; Uppsala University

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