title: Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease.
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 (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.
  
  
  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.
authors.affiliation: Exercise Health and Technology Centre, Shanghai Jiao Tong University, Shanghai, China; Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
authors.forename: Sulin
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Wiklund
authors.affiliation: Department of Signal Processing, Tampere University of Technology, Tampere, Finland; School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: Reija
authors.initials: R
authors.lastname: Autio
authors.affiliation: Department of Diagnostic Radiology, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Ronald
authors.initials: R
authors.lastname: Borra
authors.affiliation: Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ojanen
authors.affiliation: Exercise Health and Technology Centre, Shanghai Jiao Tong University, Shanghai, China; Medical School, Ningbo University, Ningbo, China.
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Törmäkangas
authors.affiliation: Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland; Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Alen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000596:Amino Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology*; D009765:Obesity / Q000378:metabolism
chemical_list: D000596:Amino Acids; D005227:Fatty Acids