Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor

Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional chara...

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Bibliographic Details
Published in:Basic research in cardiology 2017-03, Vol.112 (2), p.13-13, Article 13
Main Authors: Jovancevic, Nikolina, Dendorfer, A., Matzkies, M., Kovarova, M., Heckmann, J. C., Osterloh, M., Boehm, M., Weber, L., Nguemo, F., Semmler, J., Hescheler, J., Milting, H., Schleicher, E., Gelis, L., Hatt, H.
Format: Article
Language:English
Subjects:
Blotting, Western
Cardiology
Cells, Cultured
Fatty Acids - metabolism
Gene Knockdown Techniques
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Immunoprecipitation
Medicine
Medicine & Public Health
Myocardium - metabolism
Myocytes, Cardiac - metabolism
Neoplasm Proteins - metabolism
Original Contribution
Polymerase Chain Reaction
Receptors, G-Protein-Coupled - metabolism
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Summary:Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca 2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-017-0600-y