In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-28), p. e1009270-
Abstract:
Skeletal muscle plays a central role in regulating glucose uptake and body metabolism; however, highland hypoxia is a severe challenge to aerobic metabolism in small endotherms. Therefore, understanding the physiological and genetic convergence of muscle hypoxia tolerance has a potential broad range of medical implications. Here we report and experimentally validate a common physiological mechanism across multiple high-altitude songbirds that improvement in insulin sensitivity contributes to glucose homeostasis, low oxygen consumption, and relative activity, and thus increases body weight. By contrast, low-altitude songbirds exhibit muscle loss, glucose intolerance, and increase energy expenditures under hypoxia. This adaptive mechanism is attributable to convergent missense mutations in the BNIP3L gene, and METTL8 gene that activates MEF2C expression in highlanders, which in turn increases hypoxia tolerance. Together, our findings from wild high-altitude songbirds suggest convergent physiological and genetic mechanisms of skeletal muscle in hypoxia resistance, which highlights the potentially medical implications of hypoxia-related metabolic diseases.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1009270
DOI:
10.1371/journal.pgen.1009270.g001
DOI:
10.1371/journal.pgen.1009270.g002
DOI:
10.1371/journal.pgen.1009270.g003
DOI:
10.1371/journal.pgen.1009270.g004
DOI:
10.1371/journal.pgen.1009270.t001
DOI:
10.1371/journal.pgen.1009270.s001
DOI:
10.1371/journal.pgen.1009270.s002
DOI:
10.1371/journal.pgen.1009270.s003
DOI:
10.1371/journal.pgen.1009270.s004
DOI:
10.1371/journal.pgen.1009270.s005
DOI:
10.1371/journal.pgen.1009270.s006
DOI:
10.1371/journal.pgen.1009270.s007
DOI:
10.1371/journal.pgen.1009270.s008
DOI:
10.1371/journal.pgen.1009270.s009
DOI:
10.1371/journal.pgen.1009270.s010
DOI:
10.1371/journal.pgen.1009270.s011
DOI:
10.1371/journal.pgen.1009270.s012
DOI:
10.1371/journal.pgen.1009270.s013
DOI:
10.1371/journal.pgen.1009270.s014
DOI:
10.1371/journal.pgen.1009270.s015
DOI:
10.1371/journal.pgen.1009270.s016
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2186725-2
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