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Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study.
Physiol Rep. 2019 07; 7(13):e14165.PR

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.

Authors+Show Affiliations

Experimental and Clinical Research Center (ECRC), a Joint Institution between the Charité University Medicine, Max Delbrück Center (MDC) for Molecular Medicine, Berlin-Buch, Germany. HELIOS Klinikum Berlin-Buch, Berlin, Germany.LIPIDOMIX GmbH, Berlin, Germany.LIPIDOMIX GmbH, Berlin, Germany.Experimental and Clinical Research Center (ECRC), a Joint Institution between the Charité University Medicine, Max Delbrück Center (MDC) for Molecular Medicine, Berlin-Buch, Germany.Experimental and Clinical Research Center (ECRC), a Joint Institution between the Charité University Medicine, Max Delbrück Center (MDC) for Molecular Medicine, Berlin-Buch, Germany. Max-Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31304687

Citation

Gollasch, Benjamin, et al. "Maximal Exercise and Plasma Cytochrome P450 and Lipoxygenase Mediators: a Lipidomics Study." Physiological Reports, vol. 7, no. 13, 2019, pp. e14165.
Gollasch B, Dogan I, Rothe M, et al. Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study. Physiol Rep. 2019;7(13):e14165.
Gollasch, B., Dogan, I., Rothe, M., Gollasch, M., & Luft, F. C. (2019). Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study. Physiological Reports, 7(13), e14165. https://doi.org/10.14814/phy2.14165
Gollasch B, et al. Maximal Exercise and Plasma Cytochrome P450 and Lipoxygenase Mediators: a Lipidomics Study. Physiol Rep. 2019;7(13):e14165. PubMed PMID: 31304687.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study. AU - Gollasch,Benjamin, AU - Dogan,Inci, AU - Rothe,Michael, AU - Gollasch,Maik, AU - Luft,Friedrich C, PY - 2019/05/13/received PY - 2019/06/16/revised PY - 2019/06/18/accepted PY - 2019/7/16/entrez PY - 2019/7/16/pubmed PY - 2020/6/24/medline KW - Eicosanoids KW - exercise KW - fatty acids KW - lipidomics SP - e14165 EP - e14165 JF - Physiological reports JO - Physiol Rep VL - 7 IS - 13 N2 - 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. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/31304687/Maximal_exercise_and_plasma_cytochrome_P450_and_lipoxygenase_mediators:_a_lipidomics_study_ L2 - https://doi.org/10.14814/phy2.14165 DB - PRIME DP - Unbound Medicine ER -