Murray 2017 Abstract MITOEAGLE Barcelona

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COST Action MitoEAGLE
Metabolic adaptation to high altitude in Himalayan Sherpas.

Link: MitoEAGLE

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, Murray AJ (2017)

Event: MitoEAGLE Barcelona 2017

COST Action MitoEAGLE

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 with 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 however known. 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). When 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 in part appeared to be related to a putatively advantageous allele for the 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 impact upon our understanding of human diseases in which hypoxia is a feature.


Bioblast editor: Kandolf G O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros, UK Cambridge Murray AJ, UK London Martin DS, UK Southampton Grocott MPW


Labels: MiParea: Respiration, nDNA;cell genetics, Comparative MiP;environmental MiP 

Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Skeletal muscle 



HRR: Oxygraph-2k  Event: A2 


Affiliations

Univ Cambridge, United Kingdom