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Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice.

ABSTRACT: We examined the circulatory mechanisms underlying adaptive increases in thermogenic capacity in deer mice (Peromyscus maniculatus) native to the cold hypoxic environment at high altitudes. Deer mice from high- and low-altitude populations were born and raised in captivity to adulthood, and then acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ?4300?m). Thermogenic capacity [maximal O₂ consumption (V?_O₂,max), during cold exposure] was measured in hypoxia, along with arterial O₂ saturation (Sa_O₂ ) and heart rate (f_H). Hypoxia acclimation increased V?_O₂,max by a greater magnitude in highlanders than in lowlanders. Highlanders also had higher Sa_O₂ and extracted more O₂ from the blood per heartbeat (O₂ pulse=V?_O₂,max/f_H). Hypoxia acclimation increased f_H, O₂ pulse and capillary density in the left ventricle of the heart. Our results suggest that adaptive increases in thermogenic capacity involve integrated functional changes across the O₂ cascade that augment O₂ circulation and extraction from the blood.

SUBMITTER: Tate KB

PROVIDER: S-EPMC5665433 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice.

Tate Kevin B KB Ivy Catherine M CM Velotta Jonathan P JP Storz Jay F JF McClelland Grant B GB Cheviron Zachary A ZA Scott Graham R GR

The Journal of experimental biology 20170824 Pt 20

We examined the circulatory mechanisms underlying adaptive increases in thermogenic capacity in deer mice (Peromyscus maniculatus) native to the cold hypoxic environment at high altitudes. Deer mice from high- and low-altitude populations were born and raised in captivity to adulthood, and then acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ∼4300 m). Thermogenic capacity [maximal O2 consumption (V̇O2,max), during cold exposure] w ...[more]

PMID: 28839010

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Project description:At high-altitude, small mammals are faced with the energetic challenge of sustaining thermogenesis and aerobic exercise in spite of the reduced O2 availability. Under conditions of hypoxic cold stress, metabolic demands of shivering thermogenesis and locomotion may require enhancements in the oxidative capacity and O2 diffusion capacity of skeletal muscle to compensate for the diminished tissue O2 supply. We used common-garden experiments involving highland and lowland deer mice (Peromyscus maniculatus) to investigate the transcriptional underpinnings of genetically based population differences and plasticity in muscle phenotype. We tested highland and lowland mice that were sampled in their native environments as well as lab-raised F1 progeny of wild-caught mice. Experiments revealed that highland natives had consistently greater oxidative fiber density and capillarity in the gastrocnemius muscle. RNA sequencing analyses revealed population differences in transcript abundance for 68 genes that clustered into two discrete transcriptional modules, and a large suite of transcripts (589 genes) with plastic expression patterns that clustered into five modules. The expression of two transcriptional modules was correlated with the oxidative phenotype and capillarity of the muscle, and these phenotype-associated modules were enriched for genes involved in energy metabolism, muscle plasticity, vascular development, and cell stress response. Although most of the individual transcripts that were differentially expressed between populations were negatively correlated with muscle phenotype, several genes involved in energy metabolism (e.g., Ckmt1, Ehhadh, Acaa1a) and angiogenesis (Notch4) were more highly expressed in highlanders, and the regulators of mitochondrial biogenesis, PGC-1? (Ppargc1a) and mitochondrial transcription factor A (Tfam), were positively correlated with muscle oxidative phenotype. These results suggest that evolved population differences in the oxidative capacity and capillarity of skeletal muscle involved expression changes in a small suite of coregulated genes.

Dataset Information

Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice.

Publications

Circulatory mechanisms underlying adaptive increases in thermogenic capacity in high-altitude deer mice.

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