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Horscroft 2017 Proc Natl Acad Sci U S A
Additional label 2017-05  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Enzyme TCA cycle and matrix dehydrogenases  + , Uncoupling protein  +
Has abstract The Himalayan Sherpas, a human population
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.
an diseases in which hypoxia is a feature.  +
Has editor [[Kandolf G]]  + , [[Gnaiger E]]  +
Has info [ Open Access]  + , [ Supporting information] »[[File:O2k-brief.png|36px|link=|O2k-brief]]  +
Has publicationkeywords Metabolism  + , Altitude  + , Skeletal muscle  + , Hypoxia  + , Mitochondria  +
Has title Horscroft JA, Kotwica AO, Laner V, West JA
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) Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci U S A 114:6382–7.
tion. Proc Natl Acad Sci U S A 114:6382–7.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  + , mtDNA;mt-genetics  + , nDNA;cell genetics  + , Comparative MiP;environmental MiP  + , Exercise physiology;nutrition;life style  +
Pathways F  + , N  + , S  + , NS  + , Other combinations  +
Preparation Permeabilized tissue  +
Respiration and regulation Coupling efficiency;uncoupling  +
Stress Oxidative stress;RONS  + , Hypoxia  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab AT Innsbruck Oroboros + , AT Innsbruck Gnaiger E + , UK Cambridge Murray AJ + , UK London Martin DS + , UK Southampton Grocott MPW +
Was published in journal Proc Natl Acad Sci U S A +
Was published in year 2017  +
Was written by 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 +
Categories Publications
Modification date
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09:56:40, 10 April 2019  +
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