Horscroft 2017 Proc Natl Acad Sci U S A

From Bioblast
Revision as of 17:25, 21 January 2019 by Beno Marija (talk | contribs)
Jump to: navigation, search
Publications in the MiPMap
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.

» Open Access, Supporting information »O2k-brief

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) Proc Natl Acad Sci U S A

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.

Keywords: Metabolism, Altitude, Skeletal muscle, Hypoxia, Mitochondria Bioblast editor: Kandolf G, Gnaiger E O2k-Network Lab: AT Innsbruck Oroboros, AT Innsbruck Gnaiger E, UK Cambridge Murray AJ, UK London Martin DS, UK Southampton Grocott MPW


Labels: MiParea: Respiration, mtDNA;mt-genetics, nDNA;cell genetics, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style 

Stress:Oxidative stress;RONS, Hypoxia  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: TCA cycle and matrix dehydrogenases, Uncoupling protein  Regulation: Coupling efficiency;uncoupling  Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, Other combinations  HRR: Oxygraph-2k 

2017-05 

PNAS in this issue Sherpa.jpg

'.. it is one of the articles featured on the cover this week, and we also get top-billing in "This Week in PNAS" .. it has been brought to my attention that it was the 13th most read article in PNAS in May - not bad going for an article published on 22nd of the month.' - Andrew Murray, University Senior Lecturer in Physiology, University of Cambridge, UK


Correction

OXPHOS coupling efficiency
j≈P = (P-L)/P = OXPHOS coupling efficiency

Xtreme Everest 2

Science and adventure

Relevant links


O2k-brief

» List of O2k-Publications presented as O2k-brief