Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp
Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp
At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton (1H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively. Bayesian robust hierarchical regression revealed decreasing isoleucine with ascent alongside increasing lactate and decreasing glucose, which may point towards increased glycolytic rate. Changes in the lipid profile with ascent included a decrease in triglycerides (48-50 carbons) associated with de novo lipogenesis, alongside increases in circulating levels of the most abundant free fatty acids (palmitic, linoleic and oleic acids). Together, this may be indicative of fat store mobilisation. This study provides the first broad metabolomic account of progressive exposure to environmental hypobaric hypoxia in healthy humans. Decreased isoleucine is of particular interest as a potential contributor to muscle catabolism observed with exposure to hypoxia at altitude. Substantial changes in lipid metabolism may represent important metabolic responses to sub-acute exposure to environmental hypoxia.
2297
O'Brien, Katie A.
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Atkinson, R. Andrew
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Richardson, Larissa
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Koulman, Albert
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Murray, Andrew J.
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Harridge, Stephen D.R.
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Martin, Daniel S.
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Levett, Denny Z.H.
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Mitchell, Kay
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Mythen, Monty G.
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Montgomery, Hugh E.
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Grocott, Michael P.W.
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Griffin, Julian L.
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Edwards, Lindsay M.
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19 February 2019
O'Brien, Katie A.
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Atkinson, R. Andrew
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Richardson, Larissa
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Koulman, Albert
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Murray, Andrew J.
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Harridge, Stephen D.R.
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Martin, Daniel S.
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Levett, Denny Z.H.
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Mitchell, Kay
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Mythen, Monty G.
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Montgomery, Hugh E.
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Grocott, Michael P.W.
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Griffin, Julian L.
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Edwards, Lindsay M.
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O'Brien, Katie A., Atkinson, R. Andrew, Richardson, Larissa, Koulman, Albert, Murray, Andrew J., Harridge, Stephen D.R., Martin, Daniel S., Levett, Denny Z.H., Mitchell, Kay, Mythen, Monty G., Montgomery, Hugh E., Grocott, Michael P.W., Griffin, Julian L. and Edwards, Lindsay M.
(2019)
Metabolomic and lipidomic plasma profile changes in human participants ascending to Everest Base Camp.
Scientific Reports, 9 (1), .
(doi:10.1038/s41598-019-38832-z).
Abstract
At high altitude oxygen delivery to the tissues is impaired leading to oxygen insufficiency (hypoxia). Acclimatisation requires adjustment to tissue metabolism, the details of which remain incompletely understood. Here, metabolic responses to progressive environmental hypoxia were assessed through metabolomic and lipidomic profiling of human plasma taken from 198 human participants before and during an ascent to Everest Base Camp (5,300 m). Aqueous and lipid fractions of plasma were separated and analysed using proton (1H)-nuclear magnetic resonance spectroscopy and direct infusion mass spectrometry, respectively. Bayesian robust hierarchical regression revealed decreasing isoleucine with ascent alongside increasing lactate and decreasing glucose, which may point towards increased glycolytic rate. Changes in the lipid profile with ascent included a decrease in triglycerides (48-50 carbons) associated with de novo lipogenesis, alongside increases in circulating levels of the most abundant free fatty acids (palmitic, linoleic and oleic acids). Together, this may be indicative of fat store mobilisation. This study provides the first broad metabolomic account of progressive exposure to environmental hypobaric hypoxia in healthy humans. Decreased isoleucine is of particular interest as a potential contributor to muscle catabolism observed with exposure to hypoxia at altitude. Substantial changes in lipid metabolism may represent important metabolic responses to sub-acute exposure to environmental hypoxia.
Text
s41598-019-38832-z
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Accepted/In Press date: 10 January 2019
e-pub ahead of print date: 19 February 2019
Published date: 19 February 2019
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Local EPrints ID: 428617
URI: http://eprints.soton.ac.uk/id/eprint/428617
ISSN: 2045-2322
PURE UUID: bad44b2b-7e4e-4bc2-9c6d-ccb949b466c4
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Date deposited: 05 Mar 2019 17:30
Last modified: 16 Mar 2024 04:27
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Contributors
Author:
Katie A. O'Brien
Author:
R. Andrew Atkinson
Author:
Larissa Richardson
Author:
Albert Koulman
Author:
Andrew J. Murray
Author:
Stephen D.R. Harridge
Author:
Daniel S. Martin
Author:
Denny Z.H. Levett
Author:
Kay Mitchell
Author:
Monty G. Mythen
Author:
Hugh E. Montgomery
Author:
Julian L. Griffin
Author:
Lindsay M. Edwards
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