AUTHOR=Cas Michele Dei , Morano Camillo , Ottolenghi Sara , Dicasillati Roberto , Roda Gabriella , Samaja Michele , Paroni Rita 

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

JOURNAL=Frontiers in Physiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.819345

DOI=10.3389/fphys.2022.819345

ISSN=1664-042X

ABSTRACT=Although the human body may dynamically adapt to moderate 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 3800 m asl, the Concordia Station in Antarctica represents an opportunity to study the course of human adaption to moderate 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 analysed by untargeted LC-HR-MS 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 self-consistent 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, 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.