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

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Hyötyläinen , T , Jerby , L , Petäjä , E M , Mattila , I , Jäntti , S , Auvinen , P , Gastaldelli , A , Yki-Järvinen , H , Ruppin , E & Oresic , M 2016 , ' Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease ' , Nature Communications , vol. 7 , 8994 . https://doi.org/10.1038/ncomms9994

Title: Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease
Author: Hyötyläinen, Tuulia; Jerby, Livnat; Petäjä, Elina M.; Mattila, Ismo; Jäntti, Sirkku; Auvinen, Petri; Gastaldelli, Amalia; Yki-Järvinen, Hannele; Ruppin, Eytan; Oresic, Matej
Contributor: University of Helsinki, Clinicum
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Clinicum
Date: 2016-02
Language: eng
Number of pages: 9
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/161013
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.
Subject: DEPENDENT DIABETES-MELLITUS
MASS-SPECTROMETRY
ADIPOSE-TISSUE
ANALYSIS TOOL
GLUCONEOGENESIS
LIPOLYSIS
NETWORK
GLUCOSE
OBESITY
HUMANS
3121 Internal medicine
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