Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study

Abstract Epoxides derived from arachidonic acid (AA) are released during exercise and may contribute to vasodilation. However, exercise may also affect circulating levels of other epoxides derived from cytochromes P450 (CYP) monooxygenase and lipoxygenase (LOX) pathways, many of whose exhibit cardio...

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Main Authors: Benjamin Gollasch, Inci Dogan, Michael Rothe, Maik Gollasch, Friedrich C. Luft
Format: Article
Language:English
Published: Wiley 2019-07-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.14165
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author Benjamin Gollasch
Inci Dogan
Michael Rothe
Maik Gollasch
Friedrich C. Luft
author_facet Benjamin Gollasch
Inci Dogan
Michael Rothe
Maik Gollasch
Friedrich C. Luft
author_sort Benjamin Gollasch
collection DOAJ
description Abstract Epoxides derived from arachidonic acid (AA) are released during exercise and may contribute to vasodilation. However, exercise may also affect circulating levels of other epoxides derived from cytochromes P450 (CYP) monooxygenase and lipoxygenase (LOX) pathways, many of whose exhibit cardiovascular activity in vitro. The effects of exercise on their levels have not been documented. We tested the hypothesis that acute, maximal exercise would influence the plasma concentrations of these vasoactive substances. We measured plasma CYP and LOX mediators derived from both the n − 3 and n − 6 fatty acid (FA) classes in healthy volunteers before, during and after short‐term exhaustive exercise. Lipid mediators were profiled by means of LC–MS/MS tandem mass spectrometry. A maximal Bruce treadmill test was performed to voluntary exhaustion. Exhaustive exercise increased the circulating levels of epoxyoctadecenoic (12,13‐EpOME), dihydroxyeicosatrienoic (5,6‐DHET), dihydroxyeicosatetraenoic acids (5,6‐DiHETE, 17,18‐DiHETE), but had no effect on the majority of CYP and LOX metabolites. Although our calculations of diol/epoxide ratios revealed preferred hydrolysis of epoxyeicosatrienoic acids (EEQs) into their diols (DiHETEs), this hydrolysis was resistant to maximal exercise. Our study is the first documentation that bioactive endogenous n − 3 and n − 6 CYP lipid mediators are released by short‐term exhaustive exercise in humans. In particular, the CYP epoxy‐metabolite status, 12,13‐EpOME/DiHOME, 5,6‐EET/DHET, 5,6‐EEQ/DiHETE and 17,18‐EEQ/DiHETE may contribute to the cardiovascular response during maximal exercise.
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spelling doaj.art-89d1ce0af68e4d4497f35b671c48fa572022-12-21T18:47:49ZengWileyPhysiological Reports2051-817X2019-07-01713n/an/a10.14814/phy2.14165Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics studyBenjamin Gollasch0Inci Dogan1Michael Rothe2Maik Gollasch3Friedrich C. Luft4Experimental and Clinical Research Center (ECRC) a Joint Institution between the Charité University Medicine Max Delbrück Center (MDC) for Molecular Medicine Berlin‐Buch GermanyLIPIDOMIX GmbH Berlin GermanyLIPIDOMIX GmbH Berlin GermanyExperimental and Clinical Research Center (ECRC) a Joint Institution between the Charité University Medicine Max Delbrück Center (MDC) for Molecular Medicine Berlin‐Buch GermanyExperimental and Clinical Research Center (ECRC) a Joint Institution between the Charité University Medicine Max Delbrück Center (MDC) for Molecular Medicine Berlin‐Buch GermanyAbstract Epoxides derived from arachidonic acid (AA) are released during exercise and may contribute to vasodilation. However, exercise may also affect circulating levels of other epoxides derived from cytochromes P450 (CYP) monooxygenase and lipoxygenase (LOX) pathways, many of whose exhibit cardiovascular activity in vitro. The effects of exercise on their levels have not been documented. We tested the hypothesis that acute, maximal exercise would influence the plasma concentrations of these vasoactive substances. We measured plasma CYP and LOX mediators derived from both the n − 3 and n − 6 fatty acid (FA) classes in healthy volunteers before, during and after short‐term exhaustive exercise. Lipid mediators were profiled by means of LC–MS/MS tandem mass spectrometry. A maximal Bruce treadmill test was performed to voluntary exhaustion. Exhaustive exercise increased the circulating levels of epoxyoctadecenoic (12,13‐EpOME), dihydroxyeicosatrienoic (5,6‐DHET), dihydroxyeicosatetraenoic acids (5,6‐DiHETE, 17,18‐DiHETE), but had no effect on the majority of CYP and LOX metabolites. Although our calculations of diol/epoxide ratios revealed preferred hydrolysis of epoxyeicosatrienoic acids (EEQs) into their diols (DiHETEs), this hydrolysis was resistant to maximal exercise. Our study is the first documentation that bioactive endogenous n − 3 and n − 6 CYP lipid mediators are released by short‐term exhaustive exercise in humans. In particular, the CYP epoxy‐metabolite status, 12,13‐EpOME/DiHOME, 5,6‐EET/DHET, 5,6‐EEQ/DiHETE and 17,18‐EEQ/DiHETE may contribute to the cardiovascular response during maximal exercise.https://doi.org/10.14814/phy2.14165Eicosanoidsexercisefatty acidslipidomics
spellingShingle Benjamin Gollasch
Inci Dogan
Michael Rothe
Maik Gollasch
Friedrich C. Luft
Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
Physiological Reports
Eicosanoids
exercise
fatty acids
lipidomics
title Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
title_full Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
title_fullStr Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
title_full_unstemmed Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
title_short Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study
title_sort maximal exercise and plasma cytochrome p450 and lipoxygenase mediators a lipidomics study
topic Eicosanoids
exercise
fatty acids
lipidomics
url https://doi.org/10.14814/phy2.14165
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