Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease
Artikel i vetenskaplig tidskrift, 2014

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.

STEATOHEPATITIS

PHYSIOLOGY

GENE-EXPRESSION

NETWORK

METHIONINE

BIOMARKERS

HEPATOCELLULAR-CARCINOMA

STEATOSIS

GLOBAL RECONSTRUCTION

PREDICTION

Författare

Adil Mardinoglu

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Rasmus Ågren

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

C. Kampf

Uppsala universitet

A. Asplund

Uppsala universitet

M. Uhlen

Kungliga Tekniska Högskolan (KTH)

Jens B Nielsen

Chalmers, Kemi- och bioteknik, Livsvetenskaper, Systembiologi

Nature Communications

2041-1723 (ISSN)

Vol. 5 11-

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

Styrkeområden

Livsvetenskaper och teknik

Ämneskategorier

Kemi

DOI

10.1038/ncomms4083

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Senast uppdaterat

2018-02-28