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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
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.

2045-2322
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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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), 2297. (doi:10.1038/s41598-019-38832-z).

Record type: Article

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.

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s41598-019-38832-z - Version of Record
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More information

Accepted/In Press date: 10 January 2019
e-pub ahead of print date: 19 February 2019
Published date: 19 February 2019

Identifiers

Local EPrints ID: 428617
URI: https://eprints.soton.ac.uk/id/eprint/428617
ISSN: 2045-2322
PURE UUID: bad44b2b-7e4e-4bc2-9c6d-ccb949b466c4
ORCID for Kay Mitchell: ORCID iD orcid.org/0000-0001-6393-8475
ORCID for Michael P.W. Grocott: ORCID iD orcid.org/0000-0002-9484-7581

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Date deposited: 05 Mar 2019 17:30
Last modified: 03 Dec 2019 01:43

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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 ORCID iD
Author: Monty G. Mythen
Author: Hugh E. Montgomery
Author: Julian L. Griffin
Author: Lindsay M. Edwards

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