Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders

Eva C. Schulte, Elisabeth Altmaier, Hannah S. Berger, Kieu Trinh Do, Gabi Kastenmüller, Simone Wahl, Jerzy Adamski, Annette Peters, Jan Krumsiek, Karsten Suhre, Bernhard Haslinger, Andres Ceballos-Baumann, Christian Gieger, Juliane Winkelmann

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND: Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS) and Parkinson`s disease (PD) represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.

METHODS: 456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.

RESULTS: After stringent quality control, we identified decreased levels of long-chain (polyunsaturated) fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9) and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32). In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7). The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.

CONCLUSIONS: A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

Original languageEnglish
Pages (from-to)e0147129
JournalPLoS One
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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Restless Legs Syndrome
Inositol
Lipid Metabolism
Metabolism
legs
Parkinson Disease
Lipids
metabolism
lipids
Metabolites
blood serum
Population Control
metabolites
movement disorders
pathogenesis
Movement Disorders
dopamine
Serum
Unsaturated Fatty Acids
Biomarkers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Schulte, E. C., Altmaier, E., Berger, H. S., Do, K. T., Kastenmüller, G., Wahl, S., ... Winkelmann, J. (2016). Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders. PLoS One, 11(1), e0147129. https://doi.org/10.1371/journal.pone.0147129

Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders. / Schulte, Eva C.; Altmaier, Elisabeth; Berger, Hannah S.; Do, Kieu Trinh; Kastenmüller, Gabi; Wahl, Simone; Adamski, Jerzy; Peters, Annette; Krumsiek, Jan; Suhre, Karsten; Haslinger, Bernhard; Ceballos-Baumann, Andres; Gieger, Christian; Winkelmann, Juliane.

In: PLoS One, Vol. 11, No. 1, 01.01.2016, p. e0147129.

Research output: Contribution to journalArticle

Schulte, EC, Altmaier, E, Berger, HS, Do, KT, Kastenmüller, G, Wahl, S, Adamski, J, Peters, A, Krumsiek, J, Suhre, K, Haslinger, B, Ceballos-Baumann, A, Gieger, C & Winkelmann, J 2016, 'Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders', PLoS One, vol. 11, no. 1, pp. e0147129. https://doi.org/10.1371/journal.pone.0147129
Schulte EC, Altmaier E, Berger HS, Do KT, Kastenmüller G, Wahl S et al. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders. PLoS One. 2016 Jan 1;11(1):e0147129. https://doi.org/10.1371/journal.pone.0147129
Schulte, Eva C. ; Altmaier, Elisabeth ; Berger, Hannah S. ; Do, Kieu Trinh ; Kastenmüller, Gabi ; Wahl, Simone ; Adamski, Jerzy ; Peters, Annette ; Krumsiek, Jan ; Suhre, Karsten ; Haslinger, Bernhard ; Ceballos-Baumann, Andres ; Gieger, Christian ; Winkelmann, Juliane. / Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders. In: PLoS One. 2016 ; Vol. 11, No. 1. pp. e0147129.
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