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Koch, M.* ; Freitag-Wolf, S.* ; Schlesinger, S.* ; Borggrefe, J.* ; Hov, J.R.* ; Jensen, M.K.* ; Pick, J.* ; Markus, M.R.* ; Höpfner, T.* ; Jacobs, G.* ; Siegert, S.* ; Artati, A. ; Kastenmüller, G. ; Römisch-Margl, W. ; Adamski, J. ; Illig, T.* ; Nothnagel, M.* ; Karlsen, T.H.* ; Schreiber, S.* ; Franke, A.* ; Krawczak, M.* ; Nöthlings, U.* ; Lieb, W.*

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

Eur. J. Clin. Nutr. 71, 995–1001 (2017)

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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.European Journal of Clinical Nutrition advance online publication, 5 April 2017; doi:10.1038/ejcn.2017.43.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Hepatic Steatosis; Disease; Progression; Patterns; Metaboanalyst; Biomarkers; Systems; Risk; Tool

ISSN (print) / ISBN 0954-3007

e-ISSN 1476-5640

Journal European Journal of Clinical Nutrition

Quellenangaben Volume: 71, Issue: 8, Pages: 995–1001

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Institute of Computational Biology (ICB)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Bioinformatics and Systems Biology (IBIS)