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. 2022 Jan 25:13:819345.
doi: 10.3389/fphys.2022.819345. eCollection 2022.

Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

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Inside the Alterations of Circulating Metabolome in Antarctica: The Adaptation to Chronic Hypoxia

Michele Dei Cas et al. Front Physiol. .

Erratum in

Abstract

Although the human body may dynamically adapt to mild and brief oxygen shortages, there is a growing interest in understanding how the metabolic pathways are modified during sustained exposure to chronic hypoxia. Located at an equivalent altitude of approximately 3,800 m asl, the Concordia Station in Antarctica represents an opportunity to study the course of human adaption to mild hypoxia with reduced impact of potentially disturbing variables else than oxygen deprivation. We recruited seven healthy subjects who spent 10 months in the Concordia Station, and collected plasma samples at sea level before departure, and 90 days, 6 months, and 10 months during hypoxia. Samples were analyzed by untargeted liquid chromatography high resolution mass spectrometry to unravel how the non-polar and polar metabolomes are affected. Statistical analyses were performed by clustering the subjects into four groups according to the duration of hypoxia exposure. The non-polar metabolome revealed a modest decrease in the concentration of all the major lipid classes. By contrast, the polar metabolome showed marked alterations in several metabolic pathways, especially those related to amino acids metabolism, with a particular concern of arginine, glutamine, phenylalanine, tryptophan, and tyrosine. Remarkably, all the changes were evident since the first time point and remained unaffected by hypoxia duration (with the exception of a slight return of the non-polar metabolome after 6 months), highlighting a relative inability of the body to compensate them. Finally, we identified a few metabolic pathways that emerged as the main targets of chronic hypoxia.

Keywords: Antarctica; adaptation; chronic hypoxia; lipidomics; metabolites; metabolomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Alterations in circulating lipidome during 10 months of chronic hypoxia in the Antarctica. (A) Multivariate analysis visualized as principal discriminant analysis of lipids in plasma after 0, 90, 150–180 (MW), and 300 days (END) in the Antarctica. (B) Discriminant lipids were chosen between those with a VIP > 1.0, then ordered and summed according to their class, and finally visualized as a heat map after transformation to values of z. Data are shown as log-fold change of each time points (90, MW, END) over baseline values. The three columns on the right show the significance of the difference vs. time 0 by one-way ANOVA and the Dunnett post-hoc test. (C) Discriminant (VIP) lipids grouped in their classes and subclasses as a donut chart graph.
Figure 2
Figure 2
Alterations in the circulating polar metabolome during 10 months of chronic hypoxia in the Antarctica. (A) Multivariate analysis visualized as principal discriminant analysis of polar metabolites in plasma after 0, 90, 150–180 (MW), and 300 days (END) in Antarctica. (B) Number of identified metabolites in each subgroup: VIP, metabolites with p < 0.05 and VIP with p < 0.05. (C) Heat map of discriminant metabolites with VIP > 1.0, and at least one time point with p < 0.05 vs. time 0 after transformation to values of z. Data are shown as log-fold change of each time points (90, MW, END) over baseline. The three columns on the right show the significance of the difference vs. time 0 by one-way ANOVA and the Dunnett post-hoc test.
Figure 3
Figure 3
Schematic diagram of the most altered metabolic pathways after 90 days, MW and 9 months in Antarctica with respect to baseline. Values of p were corrected for false discovery rate. Enrichment pathway analysis was performed based on Homo sapiens KEGG pathway networks. In purple, are reported those significantly modulated by performing one-way ANOVA and the Dunnett post-hoc test; in yellow, those not modulated. For each metabolism pathway, the coverage is represented by the size of the circles, while the position on the X-axis indicates the impact in a scale from 0 to 1.
Figure 4
Figure 4
Heat map of the metabolites included in the pathways significantly affected by hypoxia for every time point. On the right, are indicated in violet those significantly modulated by performing one-way ANOVA and the Dunnett post-hoc test; in yellow, those not modulated.

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References

    1. Azad P., Stobdan T., Zhou D., Hartley I., Akbari A., Bafna V., et al. . (2017). High-altitude adaptation in humans: from genomics to integrative physiology. J. Mol. Med. 95, 1269–1282. doi: 10.1007/s00109-017-1584-7, PMID: - DOI - PMC - PubMed
    1. Beall C. M. (2007). Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc. Natl. Acad. Sci. U. S. A. 104, 8655–8660. doi: 10.1073/pnas.0701985104, PMID: - DOI - PMC - PubMed
    1. Beall C. M. (2014). Adaptation to high altitude: phenotypes and genotypes. Annu. Rev. Anthropol. 43, 251–272. doi: 10.1146/annurev-anthro-102313-030000 - DOI
    1. Beall C. M., Laskowski D., Erzurum S. C. (2012). Nitric oxide in adaptation to altitude. Free Radic. Biol. Med. 52, 1123–1134. doi: 10.1016/j.freeradbiomed.2011.12.028, PMID: - DOI - PMC - PubMed
    1. Cajka T., Smilowitz J. T., Fiehn O. (2017). Validating quantitative untargeted lipidomics across nine liquid chromatography-high-resolution mass spectrometry platforms. Anal. Chem. 89, 12360–12368. doi: 10.1021/acs.analchem.7b03404, PMID: - DOI - PubMed