Metabolic adaptation to high altitude

At high altitude, hypobaric hypoxia is a significant stress for humans and other animals, challenging oxygen homeostasis and therefore tissue metabolism. Genetic signals of physiological adaptation have been identified in human populations and nonhuman species with long-term residence at high altitude. In Tibetans, some genetic signals are linked to altered metabolic function, for example, variants in EPAS1 are associated with increased glycolysis, whilst variants in PPARA are associated with a decreased capacity for fatty acid oxidation. A number of other genetic signals that may impact on metabolism have been identified in Tibetans and other populations, although the downstream consequences are not well defined. Use of high-throughput technologies to comprehensively profile metabolic phenotype could advance understanding of the evolutionary processes conferring hypoxia tolerance at high altitude.