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Metabolomics signature associated with circulating serum selenoprotein P levels

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Abstract

Purpose

Selenoprotein P (SELENOP) has been previously related to various metabolic traits with partially conflicting results. The identification of SELENOP-associated metabolites, using an untargeted metabolomics approach, may provide novel biological insights relevant to disentangle the role of SELENOP in human health.

Methods

In this cross-sectional study, 572 serum metabolites were identified by comparing the obtained LC–MS/MS spectra with spectra stored in Metabolon’s spectra library. Serum SELENOP levels were measured in 832 men and women using an ELISA kit.

Results

Circulating SELENOP levels were associated with 24 out of 572 metabolites after accounting for the number of independent dimensions in the metabolomics data, including inverse associations with alanine, glutamate, leucine, isoleucine and valine, an unknown compound X-12063, urate and the peptides gamma-glutamyl-leucine, and N-acetylcarnosine. Positive associations were observed between SELENOP and several lipid compounds. Of the identified metabolites, each standard deviation increase in the branched-chain amino acids (isoleucine, leucine, valine), alanine and gamma-glutamyl-leucine was related to higher odds of having T2DM [OR (95% CI): 1.96 (1.41–2.73); 1.62 (1.15–2.28); 1.94 (1.45–2.60), 1.57 (1.17–2.11), and 1.52 (1.13–2.05), respectively].

Conclusions

Higher serum SELENOP levels were associated with an overall healthy metabolomics profile, which may provide further insights into potential mechanisms of SELENOP-associated metabolic disorders.

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Funding

The PopGen 2.0 network is supported by the German Federal Ministry of Education and Research [Grant Number 01EY1103]. R.d.G. is supported by the Deutsche Forschungsgemeinschaft Excellence Cluster “Inflammation at Interfaces” (Grant EXC306/2).

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Authors and Affiliations

  1. Institute of Epidemiology, Kiel University, Kiel, Germany

    Romina di Giuseppe, Gunnar Jacobs & Wolfgang Lieb

  2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Manja Koch

  3. Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany

    Ute Nöthlings

  4. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany

    Gabi Kastenmüller

  5. Deutsches Zentrum für Diabetesforschung (DZD), Neuherberg, Germany

    Gabi Kastenmüller & Jerzy Adamski

  6. Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany

    Anna Artati & Jerzy Adamski

  7. Experimental Genetics, Technical University of Munich, Freising, Germany

    Jerzy Adamski

  8. Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Gunnar Jacobs & Wolfgang Lieb

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  1. Romina di Giuseppe
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Correspondence to Romina di Giuseppe.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study procedures have been approved by the Ethics Committee of the Medical Faculty of the University of Kiel, Germany.

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di Giuseppe, R., Koch, M., Nöthlings, U. et al. Metabolomics signature associated with circulating serum selenoprotein P levels. Endocrine 64, 486–495 (2019). https://doi.org/10.1007/s12020-018-1816-9

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