Metabolic basis to Sherpa altitude adaptation

Horscroft, J.A., Kotwica, A.O., Laner, V., West, J.A., Hennis, P.J. ORCID: 0000-0002-8216-998X, Levett, D.Z.H., Howard, D.J., Fernandez, B.O., Burgess, S.L., Ament, Z., Gilbert-Kawai, E.T., Vercueil, A., Landis, B.D., Mitchell, K., Mythen, M.G., Branco, C., Johnson, R.S., Feelisch, M., Montgomery, H.E., Griffin, J.L., Grocott, M.P.W., Gnaiger, E., Martin, D.S. and Murray, A.J., 2017. Metabolic basis to Sherpa altitude adaptation. Proceedings of the National Academy of Sciences, 114 (24), pp. 6382-6387. ISSN 0027-8424

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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.

Item Type: Journal article
Publication Title: Proceedings of the National Academy of Sciences
Creators: Horscroft, J.A., Kotwica, A.O., Laner, V., West, J.A., Hennis, P.J., Levett, D.Z.H., Howard, D.J., Fernandez, B.O., Burgess, S.L., Ament, Z., Gilbert-Kawai, E.T., Vercueil, A., Landis, B.D., Mitchell, K., Mythen, M.G., Branco, C., Johnson, R.S., Feelisch, M., Montgomery, H.E., Griffin, J.L., Grocott, M.P.W., Gnaiger, E., Martin, D.S. and Murray, A.J.
Publisher: National Academy of Sciences
Date: 13 June 2017
Volume: 114
Number: 24
ISSN: 0027-8424
Identifiers:
NumberType
10.1073/pnas.1700527114DOI
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 22 Sep 2017 08:05
Last Modified: 28 Sep 2017 08:03
URI: http://irep.ntu.ac.uk/id/eprint/31659

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