Journal Article

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

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

2015

Overview

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. Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H 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. 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). 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Accumulation / Adipose tissue / Adipose Tissue - metabolism / Adipose Tissue - pathology / Amino acid metabolism / Amino acids / Amino Acids - metabolism / Biomarkers / Body fat / Cancer / Catabolism / Chain branching / Chains / Development and progression / Diabetes / DNA microarrays / Energy metabolism / Families & family life / Fatty acids / Fatty Acids - metabolism / Fatty liver / Female / Gene expression / Genetic aspects / Health aspects / Health sciences / Humans / Insulin / Insulin resistance / Liver / Liver - physiopathology / Liver diseases / Magnetic resonance / Magnetic Resonance Spectroscopy / Male / Metabolism / Metabolites / Metabolomics / Middle Aged / Mitochondria / Morbidity / Muscles / Musculoskeletal system / NMR / Non-alcoholic Fatty Liver Disease - metabolism / Non-alcoholic Fatty Liver Disease - pathology / Nuclear magnetic resonance / Obesity / Obesity - metabolism / Pathogenesis / Physiological aspects / Proton magnetic resonance / Resonance / Risk factors / Rodents / Skeletal muscle / Spectroscopy / Studies / Womens health