Journal
SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-38832-z
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Funding
- BOC Medical part of the Linde Group
- Ely-Lilly Critical Care
- London Clinic (a private hospital)
- Smiths Medical
- Deltex Medical
- Rolex
- Association of Anaesthetists of Great Britain and Ireland
- UK Intensive Care Foundation
- National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, London, UK
- National Institute of Health Research (NIHR) University Hospital Southampton Biomedical Research Centre, Southampton, UK
- Academic Fellowship from the Research Councils UK [EP/E500552/1]
- Medical Research Council [MC_UP_A090_1006]
- King's College London on a Graduate Teaching Assistant PhD studentship
- BBSRC [BB/P028195/1, BB/M027252/1, BB/M027252/2] Funding Source: UKRI
- MRC [MC_PC_13030, MR/P011705/1, MC_UU_12012/5, MC_UP_A090_1006, MR/P01836X/1] Funding Source: UKRI
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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 (H-1)-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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