期刊
EUROPEAN JOURNAL OF CLINICAL NUTRITION
卷 71, 期 8, 页码 995-1001出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejcn.2017.43
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资金
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) Excellence Cluster 'Inflammation at Interfaces' [EXC306, EXC306/2]
- sysINFLAME [01ZX1306A]
- German Federal Ministry of Education and Research [01GR0468]
- German Ministry for Education and Research [01EY1103]
- DFG [KO 5187/1-1]
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.
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