Koch, M., Freitag-Wolf, S., Schlesinger, S., Borggrefe, J., Hov, J. R., Jensen, M. K., Pick, J., Markus, M. R. P., Hoepfner, T., Jacobs, G., Siegert, S., Artati, A., Kastenmueller, G., Roemisch-Margl, W., Adamski, J., Illig, T., Nothnagel, M., Karlsen, T. H., Schreiber, S., Franke, A., Krawczak, M., Noethlings, U. and Lieb, W. (2017). Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample. Eur. J. Clin. Nutr., 71 (8). S. 995 - 1002. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5640

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Abstract

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 41 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koch, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freitag-Wolf, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlesinger, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borggrefe, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hov, J. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, M. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pick, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Markus, M. R. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoepfner, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jacobs, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siegert, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Artati, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kastenmueller, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roemisch-Margl, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adamski, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illig, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothnagel, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karlsen, T. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krawczak, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethlings, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lieb, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-223165
DOI: 10.1038/ejcn.2017.43
Journal or Publication Title: Eur. J. Clin. Nutr.
Volume: 71
Number: 8
Page Range: S. 995 - 1002
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5640
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEPATIC STEATOSIS; DISEASE; PATTERNS; PROGRESSION; BIOMARKERS; RISK; TOOLMultiple languages
Nutrition & DieteticsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22316

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