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Serum metabolomic profiling highlights pathways associated with liver fat content in a general population sample.
Koch, M; Freitag-Wolf, S; Schlesinger, S; Borggrefe, J; Hov, J R; Jensen, M K; Pick, J; Markus, M R P; 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.
Afiliación
  • Koch M; Institute of Epidemiology, Kiel University, Kiel, Germany.
  • Freitag-Wolf S; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Schlesinger S; Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
  • Borggrefe J; Institute of Epidemiology, Kiel University, Kiel, Germany.
  • Hov JR; Department of Radiology, University of Cologne, Cologne, MA, USA.
  • Jensen MK; Division of Cancer Medicine, Department of Transplantation Medicine, Surgery and Transplantation, Norwegian PSC Research Center, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Pick J; K.G. Jebsen Inflammation Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • Markus MRP; Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
  • Höpfner T; Division of Cancer Medicine, Section of Gastroenterology, Department of Transplantation Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
  • Jacobs G; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Siegert S; Nutritional Epidemiology, Department of Nutrition and Food Science, Rheinische Friedrich-Wilhelms-University Bonn, Bonn, Germany.
  • Artati A; Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
  • Kastenmüller G; DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
  • Römisch-Margl W; Department of Study of Health in Pomerania/Clinical-Epidemiological Research, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Adamski J; Institute of Epidemiology, Kiel University, Kiel, Germany.
  • Illig T; Institute of Epidemiology, Kiel University, Kiel, Germany.
  • Nothnagel M; PopGen Biobank, University Medical Center Schleswig-Holstein, Kiel, Germany.
  • Karlsen TH; Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • Schreiber S; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
  • Franke A; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Krawczak M; Deutsches Zentrum für Diabetesforschung (DZD), German Centere for Diabetes Research, Neuherberg, Germany.
  • Nöthlings U; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
  • Lieb W; Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.
Eur J Clin Nutr ; 71(8): 995-1001, 2017 08.
Article en En | MEDLINE | ID: mdl-28378853
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metabolismo de los Lípidos / Hígado Graso Alcohólico / Enfermedad del Hígado Graso no Alcohólico / Hígado Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metabolismo de los Lípidos / Hígado Graso Alcohólico / Enfermedad del Hígado Graso no Alcohólico / Hígado Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido