Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "Horscroft 2017 Proc Natl Acad Sci U S A"

From Bioblast
Line 7: Line 7:
|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.
|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
|keywords=Metabolism, Altitude, Skeletal muscle, Hypoxia, Mitochondria
|editor=[[Kandolf G]],
|editor=[[Kandolf G]]
|mipnetlab=AT Innsbruck OROBOROS, AT Innsbruck Gnaiger E
|mipnetlab=AT Innsbruck OROBOROS, AT Innsbruck Gnaiger E, UK Cambridge Murray AJ, UK London Martin D
}}
}}
{{Labeling
{{Labeling
Line 21: Line 21:
|pathways=F, N, S, NS, Other combinations
|pathways=F, N, S, NS, Other combinations
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Labels, 2017-05,
|additional=Labels, 2017-05
}}
}}
== Xtreme Everest 2 ==
== Xtreme Everest 2 ==
::::* [[Xtreme Everest 2 |Picture gallery of the expedition to Everest Base Camp]]
::::* [[Xtreme Everest 2 |Picture gallery of the expedition to Everest Base Camp]]
== Links ==
::::* [http://www.cam.ac.uk/research/news/himalayan-powerhouses-how-sherpas-have-evolved-superhuman-energy-efficiency Himalayan powerhouses how sherpas have evolved superhuman energy efficiency]
::::* [http://www.bbc.co.uk/news/science-environment-40006803 Lean-burn physiology gives Sherpas peak-performance]
::::* [https://www.youtube.com/watch?v=QG7j_oue2_w How Sherpas have evolved ‘superhuman’ energy efficiency]

Revision as of 14:12, 23 May 2017

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 [Epub ahead of print].

» Open Access

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 O2k-Network Lab: AT Innsbruck OROBOROS, AT Innsbruck Gnaiger E, UK Cambridge Murray AJ, UK London Martin D


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

Stress:Oxidative stress;RONS  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, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.  Pathway: F, N, S, NS, Other combinations  HRR: Oxygraph-2k 

Labels, 2017-05 

Xtreme Everest 2

Links