oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease
Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland.
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland.
Show others and affiliations
2016 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, 8994Article in journal (Refereed) Published
Abstract [en]

Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.

Place, publisher, year, edition, pages
London, United Kingdom: Nature Publishing Group, 2016. Vol. 7, 8994
National Category
Medical and Health Sciences Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-59357DOI: 10.1038/ncomms9994ISI: 000371140200001PubMedID: 26839171Scopus ID: 2-s2.0-84957575229OAI: oai:DiVA.org:oru-59357DiVA: diva2:1135894
Funder
EU, Horizon 2020, 634413
Note

Funding Agencies:

EU FP6 project HEPADIP, Projektnr: LSHM-CT-2005-018734

Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research-SyMMyS, Projektnr: 250114

Edmond J. Safra program in bioinformatics in TAU

Israeli Science Foundation

EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF), Projektnr: 115372

Available from: 2017-08-24 Created: 2017-08-24 Last updated: 2017-09-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Oresic, Matej
In the same journal
Nature Communications
Medical and Health SciencesEndocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 12 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf