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

Content Provider	PubMed Central
Author	Hyötyläinen, Tuulia Livnat, Jerby Petäjä, Elina M. Mattila, Ismo Jäntti, Sirkku Auvinen, Petri Gastaldelli, Amalia Yki-järvinen, Hannele Ruppin, Eytan Orešič, Matej
Copyright Year	2016
Abstract	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.
Related Links	http://dx.doi.org/10.1038/ncomms9994
Starting Page	8994
File Format	PDF
ISSN	20411723
e-ISSN	20411723
Journal	Nature Communications
Volume Number	7
Language	English
Publisher	Nature Publishing Group
Publisher Date	2016-02-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) Chemistry(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Physics and Astronomy Biochemistry, Genetics and Molecular Biology

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