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Metabolic basis to Sherpa altitude adaptation

Horscroft, JA; Kotwica, AO; Laner, V; West, JA; Hennis, PJ; Levett, DZH; Howard, DJ; ... Murray, AJ; + view all (2017) Metabolic basis to Sherpa altitude adaptation. Proceedings of the National Academy of Sciences of the United States of America , 114 (24) pp. 6382-6387. 10.1073/pnas.1700527114. Green open access

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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.

Type: Article
Title: Metabolic basis to Sherpa altitude adaptation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1700527114
Publisher version: http://dx.doi.org/10.1073/pnas.1700527114
Language: English
Additional information: This version is the author accepted manuscript. The article is freely available online through the PNAS open access option; for information on re-use, please refer to the publisher’s terms and conditions.
Keywords: metabolism; altitude; skeletal muscle; hypoxia; mitochondria
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
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URI: https://discovery.ucl.ac.uk/id/eprint/1553218
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