Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System

Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Internal Mail 710 Geert Grooteplein 10, 6500HB Nijmegen, The Netherlands

Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Internal Mail 710 Geert, Grooteplein 10, 6500HB Nijmegen, The Netherlands

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Internal Mail 710 Geert Grooteplein 10, 6500HB Nijmegen, The Netherlands

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Institute of Microbiology, Technische Universität Braunschweig, Universitätsplatz 2, 38106 Braunschweig, Germany

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Metabolomic Discoveries, GmbH, Am Mühlenberg 11, 14476 Potsdam, Germany

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Department of Biochemistry and Biology, Universität Potsdam, Am Neuen Palais 10, 14469 Potsdam, Germany

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Max Planck Institute für Molekulare Pflanzenphysiologie, Am Mühlenberg 1, 14476 Potsdam, Germany

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Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Droevendaalsesteeg 4, 6708 PB Wageningen, The Netherlands

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Immunology and Metabolism, LIMES Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2020, 10(4), 148; https://doi.org/10.3390/metabo10040148

Received: 20 February 2020 / Revised: 3 April 2020 / Accepted: 7 April 2020 / Published: 10 April 2020

(This article belongs to the Special Issue Regulation of Immunity and Inflammation by Immunometabolites and Metabolic Enzymes)

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Abstract

We recently demonstrated that the sympathetic nervous system can be voluntarily activated following a training program consisting of cold exposure, breathing exercises, and meditation. This resulted in profound attenuation of the systemic inflammatory response elicited by lipopolysaccharide (LPS) administration. Herein, we assessed whether this training program affects the plasma metabolome and if these changes are linked to the immunomodulatory effects observed. A total of 224 metabolites were identified in plasma obtained from 24 healthy male volunteers at six timepoints, of which 98 were significantly altered following LPS administration. Effects of the training program were most prominent shortly after initiation of the acquired breathing exercises but prior to LPS administration, and point towards increased activation of the Cori cycle. Elevated concentrations of lactate and pyruvate in trained individuals correlated with enhanced levels of anti-inflammatory interleukin (IL)-10. In vitro validation experiments revealed that co-incubation with lactate and pyruvate enhances IL-10 production and attenuates the release of pro-inflammatory IL-1β and IL-6 by LPS-stimulated leukocytes. Our results demonstrate that practicing the breathing exercises acquired during the training program results in increased activity of the Cori cycle. Furthermore, this work uncovers an important role of lactate and pyruvate in the anti-inflammatory phenotype observed in trained subjects. View Full-Text

Keywords: metabolomics; LPS; endotoxin; pyruvate; lactate; cytokines; inflammation; human endotoxemia; cori cycle; warburg effect

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Supplementary Materials

Supplementary File 1:
Externally hosted supplementary file 1
Doi: 10.21228/M8C671
Link: https://www.metabolomicsworkbench.org/data/DRCCMetadata.php?Mode=Study&StudyID=ST001251
Description: Metabolomics dataset.

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MDPI and ACS Style

Zwaag, J.; ter Horst, R.; Blaženović, I.; Stoessel, D.; Ratter, J.; Worseck, J.M.; Schauer, N.; Stienstra, R.; Netea, M.G.; Jahn, D.; Pickkers, P.; Kox, M. Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System. Metabolites 2020, 10, 148. https://doi.org/10.3390/metabo10040148

AMA Style

Zwaag J, ter Horst R, Blaženović I, Stoessel D, Ratter J, Worseck JM, Schauer N, Stienstra R, Netea MG, Jahn D, Pickkers P, Kox M. Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System. Metabolites. 2020; 10(4):148. https://doi.org/10.3390/metabo10040148

Chicago/Turabian Style

Zwaag, Jelle, Rob ter Horst, Ivana Blaženović, Daniel Stoessel, Jacqueline Ratter, Josephine M. Worseck, Nicolas Schauer, Rinke Stienstra, Mihai G. Netea, Dieter Jahn, Peter Pickkers, and Matthijs Kox. 2020. "Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System" Metabolites 10, no. 4: 148. https://doi.org/10.3390/metabo10040148

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Involvement of Lactate and Pyruvate in the Anti-Inflammatory Effects Exerted by Voluntary Activation of the Sympathetic Nervous System

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