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Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Menni, Cristina 
McCallum, Linsay 
Zierer, Jonas 
Aman, Alisha 

Abstract

Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10-5), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.

Description

Keywords

Acid-Base Equilibrium, Adult, Aged, Electrolytes, Female, Homeostasis, Humans, Male, Metabolic Networks and Pathways, Metabolome, Metabolomics, Middle Aged, Reproducibility of Results, Twins, United Kingdom

Journal Title

Scientific Reports

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

9

Publisher

Nature Publishing Group
Sponsorship
Includes MRC, BHF, Wellcome Trust and NIHR.