Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Sulin Cheng; Petri Wiklund; Reija Autio; Ronald Borra; Xiaowei Ojanen; Leiting Xu; Timo Törmäkangas; Markku Alen

doi:10.1371/journal.pone.0138889

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Sulin Cheng, Petri Wiklund, Reija Autio, Ronald Borra, Xiaowei Ojanen, Leiting Xu, Timo Törmäkangas, Markku Alen

Research output: Contribution to journal › Article › Scientific › peer-review

77 Citations (Scopus)

Abstract

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 (H-1 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

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.

Original language	English
Article number	0138889
Number of pages	17
Journal	PLoS ONE
Volume	10
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0138889
Publication status	Published - 2015
Publication type	A1 Journal article-refereed

Funding

The study funding is supported by various sources: The academy of Finland SKID-KIDS program (No. 135038); Shanghai Jiao Tong University Zhiyuan Foundation (CP2014013); China State Sport General Adiministration (No: 2013B040); and EVO research grants 2012/2013 from Oulu University Hospital.

Keywords

BODY-COMPOSITION
GIRLS
MAGNETIC-RESONANCE
MUSCLE INSULIN-RESISTANCE
SKELETAL-MUSCLE
WOMEN
hepatic steatosis
inflammation
obesity
pathogenesis

Publication forum classification

Publication forum level 1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0138889

Cite this

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title = "Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease",

abstract = "BackgroundFatty 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.MethodsHepatic fat content was measured using proton magnetic resonance spectroscopy (H-1 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.ResultsIncreased 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 (pConclusionsLiver 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.",

keywords = "BODY-COMPOSITION, GIRLS, MAGNETIC-RESONANCE, MUSCLE INSULIN-RESISTANCE, SKELETAL-MUSCLE, WOMEN, hepatic steatosis, inflammation, obesity, pathogenesis, BODY-COMPOSITION, GIRLS, MAGNETIC-RESONANCE, MUSCLE INSULIN-RESISTANCE, SKELETAL-MUSCLE, WOMEN, hepatic steatosis, inflammation, obesity, pathogenesis",

author = "Sulin Cheng and Petri Wiklund and Reija Autio and Ronald Borra and Xiaowei Ojanen and Leiting Xu and Timo T{\"o}rm{\"a}kangas and Markku Alen",

year = "2015",

doi = "10.1371/journal.pone.0138889",

language = "English",

volume = "10",

number = "10",

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T1 - Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

AU - Cheng, Sulin

AU - Wiklund, Petri

AU - Autio, Reija

AU - Borra, Ronald

AU - Ojanen, Xiaowei

AU - Xu, Leiting

AU - Törmäkangas, Timo

AU - Alen, Markku

PY - 2015

Y1 - 2015

N2 - BackgroundFatty 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.MethodsHepatic fat content was measured using proton magnetic resonance spectroscopy (H-1 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.ResultsIncreased 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 (pConclusionsLiver 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.

AB - BackgroundFatty 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.MethodsHepatic fat content was measured using proton magnetic resonance spectroscopy (H-1 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.ResultsIncreased 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 (pConclusionsLiver 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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KW - obesity

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KW - SKELETAL-MUSCLE

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U2 - 10.1371/journal.pone.0138889

DO - 10.1371/journal.pone.0138889

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ER -

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Abstract

Funding

Keywords

Publication forum classification

UN SDGs

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