Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease
Cheng, S., Wiklund, P., Autio, R., Borra, R., Ojanen, X., Xu, L., Törmäkangas, T., & Alén, M. (2015). Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease. PLoS ONE, 10(10), Article e0138889. https://doi.org/10.1371/journal.pone.0138889
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PLoS ONEAuthors
Date
2015Discipline
Gerontologia ja kansanterveysLiikuntalääketiedeGerontology and Public HealthSports and Exercise MedicineCopyright
© 2015 Cheng et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
Background
Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study
was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-
year-old men (n = 49) and women (n = 52) with and without NAFLD.
Methods
Hepatic fat content was measured using proton magnetic resonance spectroscopy (1
H
MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics
platform. Global gene expression profiles of adipose tissues and skeletal muscle
were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression
was analyzed by Western blot.
Results
Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid
were associated with liver fat accumulation already in its early stage, independent of
sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA
catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the
NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle
was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA
and liver fat content (p<0.05 for all). Conclusions
Liver fat accumulation, already in its early stage, is associated with increased serum
branched-chain and aromatic amino acids. The observed associations of decreased BCAA
catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with
liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic
nature of NAFLD pathogenesis.
...
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Public Library of ScienceISSN Search the Publication Forum
1932-6203Publication in research information system
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License
Except where otherwise noted, this item's license is described as © 2015 Cheng et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are
credited.
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