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The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

Vaughn, David and Brogioli, Michael and Maier, Thomas and White, Andy and Waldron, Sarah and Rittweger, Jörn and Toigo, Marco and Wettstein, Jessica and Laczko, Endre and Flück, Martin (2016) The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism. PLoS One, 11 (3), pp. 1-20. Public Library of Science (PLoS). DOI: 10.1371/journal.pone.0149046 ISSN 1932-6203

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Abstract

Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic Fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24%vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of glucose Import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism.

Item URL in elib:https://elib.dlr.de/107357/
Document Type:Article
Title:The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Vaughn, DavidInstitute for Biomedical Research into Human Movement and Health, Manchester Metropolitan UniversitUNSPECIFIED
Brogioli, MichaelInstitute for Biomedical Research into Human Movement and Health, Manchester Metropolitan UniversityUNSPECIFIED
Maier, ThomasInstitute for Biomedical Research into Human Movement and Health, Manchester Metropolitan UniversityUNSPECIFIED
White, AndyChester Marathon, Chester, United KingdomUNSPECIFIED
Waldron, SarahInstitute for Biomedical Research into Human Movement and Health, Manchester Metropolitan UniversityUNSPECIFIED
Rittweger, JörnInstitute of Aerospace Medicine, Deutsches Zentrum für Luft- und Raumfahrt, DLR e.V., Cologne, Germany and Medical Faculty, University of Cologne, Cologne, Germany; joern.rittweger (at) dlr.deUNSPECIFIED
Toigo, MarcoUniversity Hospital BalgristUNSPECIFIED
Wettstein, JessicaUniversity Hospital BalgristUNSPECIFIED
Laczko, EndreFunctional Genomics Center ZürichUNSPECIFIED
Flück, MartinUniversity, ManchesterUNSPECIFIED
Date:16 March 2016
Journal or Publication Title:PLoS One
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:11
DOI :10.1371/journal.pone.0149046
Page Range:pp. 1-20
Editors:
EditorsEmail
Motta, AndreaNational Research Council of
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Status:Published
Keywords:Exercise Metabolism; Genotype; ACE-I/D; Polymorphism
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Integrative Studien (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Space Physiology
Deposited By: Becker, Christine
Deposited On:09 Nov 2016 10:22
Last Modified:08 Mar 2018 18:49

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