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Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease

Hyötyläinen, Tuulia, 1971- (författare)
Örebro universitet,Institutionen för naturvetenskap och teknik,Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland
Jerby, Livnat (författare)
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
Petäjä, Elina M. (författare)
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
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Mattila, Ismo (författare)
Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark; VTT Technical Research Centre of Finland, Espoo, Finland
Jäntti, Sirkku (författare)
VTT Technical Research Centre of Finland, Espoo, Finland; Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
Auvinen, Petri (författare)
Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
Gastaldelli, Amalia (författare)
Institute of Clinical Physiology, National Research Council, Pisa, Italy
Yki-Järvinen, Hannele (författare)
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
Ruppin, Eytan (författare)
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel; Center for BioInformatics and Computational Biology, Department of Computer Science, University of Maryland, Maryland, USA
Oresic, Matej, 1967- (författare)
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
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 (creator_code:org_t)
2016-02-03
2016
Engelska.
Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
Relaterad länk:
https://doi.org/10.1...
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https://www.nature.c...
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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