Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample

Eur J Clin Nutr. 2017 Aug;71(8):995-1001. doi: 10.1038/ejcn.2017.43. Epub 2017 Apr 5.


Background/objectives: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD.

Subjects/methods: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses.

Results: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD.

Conclusions: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol Drinking / adverse effects
  • Biological Specimen Banks
  • Biomarkers / blood
  • Cohort Studies
  • Computational Biology
  • Cross-Sectional Studies
  • Dipeptides / blood
  • Expert Systems
  • Fatty Liver, Alcoholic / blood*
  • Fatty Liver, Alcoholic / diagnostic imaging
  • Fatty Liver, Alcoholic / metabolism
  • Fatty Liver, Alcoholic / physiopathology
  • Female
  • Glutamic Acid / analogs & derivatives
  • Glutamic Acid / blood
  • Humans
  • Lipid Metabolism*
  • Liver / diagnostic imaging
  • Liver / metabolism*
  • Liver / physiopathology
  • Magnetic Resonance Imaging
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diagnostic imaging
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Self Report
  • Severity of Illness Index


  • Biomarkers
  • Dipeptides
  • Glutamic Acid