Metabolite profiling reveals new insights into the regulation of serum urate in humans

Eva Albrecht, Melanie Waldenberger, Jan Krumsiek, Anne M. Evans, Ulli Jeratsch, Michaela Breier, Jerzy Adamski, Wolfgang Koenig, Sonja Zeilinger, Christiane Fuchs, Norman Klopp, Fabian J. Theis, H. Erich Wichmann, Karsten Suhre, Thomas Illig, Konstantin Strauch, Annette Peters, Christian Gieger, Gabi Kastenmüller, Angela DoeringChrista Meisinger

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum urate levels highly differ between men and women; however the underlying biological processes in its regulation are still not completely understood and are assumed to result from a complex interplay between genetic, environmental and lifestyle factors. In order to describe the metabolic vicinity of serum urate, we analyzed 355 metabolites in 1,764 individuals of the population-based KORA F4 study and constructed a metabolite network around serum urate using Gaussian Graphical Modeling in a hypothesis-free approach. We subsequently investigated the effect of sex and urate lowering medication on all 38 metabolites assigned to the network. Within the resulting network three main clusters could be detected around urate, including the well-known pathway of purine metabolism, as well as several dipeptides, a group of essential amino acids, and a group of steroids. Of the 38 assigned metabolites, 25 showed strong differences between sexes. Association with uricostatic medication intake was not only confined to purine metabolism but seen for seven metabolites within the network. Our findings highlight pathways that are important in the regulation of serum urate and suggest that dipeptides, amino acids, and steroid hormones are playing a role in its regulation. The findings might have an impact on the development of specific targets in the treatment and prevention of hyperuricemia.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalMetabolomics
Volume10
Issue number1
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Fingerprint

Metabolites
Uric Acid
Serum
Metabolism
Dipeptides
Steroid hormones
Steroids
Biological Phenomena
Hyperuricemia
Essential Amino Acids
Gout
Medical problems
Sex Characteristics
Type 2 Diabetes Mellitus
Life Style
Cardiovascular Diseases
Hormones
Amino Acids
Population
purine

Keywords

  • Allopurinol
  • Gaussian Graphical Modeling
  • Metabolite network
  • Pathway reconstruction
  • Purine metabolism
  • Uric acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Albrecht, E., Waldenberger, M., Krumsiek, J., Evans, A. M., Jeratsch, U., Breier, M., ... Meisinger, C. (2014). Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics, 10(1), 141-151. https://doi.org/10.1007/s11306-013-0565-2

Metabolite profiling reveals new insights into the regulation of serum urate in humans. / Albrecht, Eva; Waldenberger, Melanie; Krumsiek, Jan; Evans, Anne M.; Jeratsch, Ulli; Breier, Michaela; Adamski, Jerzy; Koenig, Wolfgang; Zeilinger, Sonja; Fuchs, Christiane; Klopp, Norman; Theis, Fabian J.; Wichmann, H. Erich; Suhre, Karsten; Illig, Thomas; Strauch, Konstantin; Peters, Annette; Gieger, Christian; Kastenmüller, Gabi; Doering, Angela; Meisinger, Christa.

In: Metabolomics, Vol. 10, No. 1, 02.2014, p. 141-151.

Research output: Contribution to journalArticle

Albrecht, E, Waldenberger, M, Krumsiek, J, Evans, AM, Jeratsch, U, Breier, M, Adamski, J, Koenig, W, Zeilinger, S, Fuchs, C, Klopp, N, Theis, FJ, Wichmann, HE, Suhre, K, Illig, T, Strauch, K, Peters, A, Gieger, C, Kastenmüller, G, Doering, A & Meisinger, C 2014, 'Metabolite profiling reveals new insights into the regulation of serum urate in humans', Metabolomics, vol. 10, no. 1, pp. 141-151. https://doi.org/10.1007/s11306-013-0565-2
Albrecht E, Waldenberger M, Krumsiek J, Evans AM, Jeratsch U, Breier M et al. Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics. 2014 Feb;10(1):141-151. https://doi.org/10.1007/s11306-013-0565-2
Albrecht, Eva ; Waldenberger, Melanie ; Krumsiek, Jan ; Evans, Anne M. ; Jeratsch, Ulli ; Breier, Michaela ; Adamski, Jerzy ; Koenig, Wolfgang ; Zeilinger, Sonja ; Fuchs, Christiane ; Klopp, Norman ; Theis, Fabian J. ; Wichmann, H. Erich ; Suhre, Karsten ; Illig, Thomas ; Strauch, Konstantin ; Peters, Annette ; Gieger, Christian ; Kastenmüller, Gabi ; Doering, Angela ; Meisinger, Christa. / Metabolite profiling reveals new insights into the regulation of serum urate in humans. In: Metabolomics. 2014 ; Vol. 10, No. 1. pp. 141-151.
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