1. Metabolic basis to Sherpa altitude adaptation.
- Author
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Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, and Murray AJ
- Subjects
- Adult, Atmospheric Pressure, Citric Acid Cycle, Energy Metabolism, Fatty Acids metabolism, Female, Gene Frequency, Glucose metabolism, Glycolysis, Humans, Hypoxia genetics, Hypoxia physiopathology, Male, Mitochondria, Muscle metabolism, Muscle, Skeletal metabolism, Nepal, Nitric Oxide blood, Oxidative Phosphorylation, Oxidative Stress, Oxygen Consumption, PPAR alpha genetics, PPAR alpha metabolism, Polymorphism, Single Nucleotide, Tibet ethnology, Adaptation, Physiological genetics, Altitude, Ethnicity genetics, Hypoxia metabolism
- Abstract
The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A ( PPARA ) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature., Competing Interests: Conflict of interest statement: E.G. is Chief Executive Officer and V.L. is Chief Operating Officer of Oroboros Instruments.
- Published
- 2017
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