PMID- 38372126 OWN - NLM STAT- MEDLINE DCOM- 20240319 LR - 20240319 IS - 1522-1490 (Electronic) IS - 0363-6119 (Linking) VI - 326 IP - 4 DP - 2024 Apr 1 TI - Evolved changes in phenotype across skeletal muscles in deer mice native to high altitude. PG - R297-R310 LID - 10.1152/ajpregu.00206.2023 [doi] AB - The cold and hypoxic conditions at high altitude necessitate high metabolic O(2) demands to support thermogenesis while hypoxia reduces O(2) availability. Skeletal muscles play key roles in thermogenesis, but our appreciation of muscle plasticity and adaptation at high altitude has been hindered by past emphasis on only a small number of muscles. We examined this issue in deer mice (Peromyscus maniculatus). Mice derived from both high-altitude and low-altitude populations were born and raised in captivity and then acclimated as adults to normoxia or hypobaric hypoxia (12 kPa O(2) for 6-8 wk). Maximal activities of citrate synthase (CS), cytochrome c oxidase (COX), beta-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured in 20 muscles involved in shivering, locomotion, body posture, ventilation, and mastication. Principal components analysis revealed an overall difference in muscle phenotype between populations but no effect of hypoxia acclimation. High-altitude mice had greater activities of mitochondrial enzymes and/or lower activities of PK or LDH across many (but not all) respiratory, limb, core and mastication muscles compared with low-altitude mice. In contrast, chronic hypoxia had very few effects across muscles. Further examination of CS in the gastrocnemius showed that population differences in enzyme activity stemmed from differences in protein abundance and mRNA expression but not from population differences in CS amino acid sequence. Overall, our results suggest that evolved increases in oxidative capacity across many skeletal muscles, at least partially driven by differences in transcriptional regulation, may contribute to high-altitude adaptation in deer mice.NEW & NOTEWORTHY Most previous studies of muscle plasticity and adaptation in high-altitude environments have focused on a very limited number of skeletal muscles. Comparing high-altitude versus low-altitude populations of deer mice, we show that a large number of muscles involved in shivering, locomotion, body posture, ventilation, and mastication exhibit greater mitochondrial enzyme activities in the high-altitude population. Therefore, evolved increases in mitochondrial oxidative capacity across skeletal muscles contribute to high-altitude adaptation. FAU - Garrett, Emily J AU - Garrett EJ AD - Department of Biology, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 FAU - Prasad, Srikripa K AU - Prasad SK AD - Department of Biology, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 FAU - Schweizer, Rena M AU - Schweizer RM AD - Division of Biological Sciences, University of Montana, Missoula, Montana, United States. AD - United States Department of Agriculture, Agricultural Research Service, Pollinating Insects Research Unit, Utah State University, Logan, Utah, United States. FAU - McClelland, Grant B AU - McClelland GB AUID- ORCID: 0000-0003-1500-9983 AD - Department of Biology, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 FAU - Scott, Graham R AU - Scott GR AUID- ORCID: 0000-0002-4225-7475 AD - Department of Biology, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 LA - eng GR - RGPIN-2018-05707/Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ GR - RGPIN-462246-2014/Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ PT - Journal Article DEP - 20240219 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 SB - IM MH - Animals MH - *Altitude MH - *Peromyscus/physiology MH - Hypoxia/metabolism MH - Muscle, Skeletal/metabolism MH - Acclimatization MH - Phenotype OTO - NOTNLM OT - acclimatization OT - evolutionary physiology OT - high elevation OT - muscle metabolism OT - shivering thermogenesis EDAT- 2024/02/19 06:42 MHDA- 2024/03/19 06:44 CRDT- 2024/02/19 05:29 PHST- 2024/03/19 06:44 [medline] PHST- 2024/02/19 06:42 [pubmed] PHST- 2024/02/19 05:29 [entrez] AID - 10.1152/ajpregu.00206.2023 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2024 Apr 1;326(4):R297-R310. doi: 10.1152/ajpregu.00206.2023. Epub 2024 Feb 19.