Abstract
Physical inactivity generates muscle atrophy in most mammalian species. In contrast, hibernating mammals demonstrate limited muscle loss over the prolonged intervals of immobility during winter, which suggests that they have adaptive mechanisms to reduce disuse muscle atrophy. To identify transcriptional programs that underlie molecular mechanisms attenuating muscle loss, we conducted a large-scale gene expression profiling in quadriceps muscle of arctic ground squirrels, comparing hibernating (late in a torpor and during torpor re-entry after arousal) and summer active animals using next generation sequencing of the transcriptome. Gene set enrichment analysis showed a coordinated up-regulation of genes involved in all stages of protein biosynthesis and ribosome biogenesis during both stages of hibernation that suggests induction of translation during interbout arousals. Elevated proportion of down-regulated genes involved in apoptosis, NFKB signaling as well as significant under expression of atrogenes, upstream regulators (FOXO1, FOXO3, NFKB1A), key components of the ubiquitin proteasome pathway (FBXO32, TRIM63, CBLB), and overexpression of PPARGC1B inhibiting proteolysis imply suppression of protein degradation in muscle during arousals. The induction of protein biosynthesis and decrease in protein catabolism likely contribute to the attenuation of disuse muscle atrophy through prolonged periods of immobility of hibernation.
Highlights
Physical inactivity generates muscle atrophy in most mammalian species
Out of 40 million paired-end sequencing reads obtained for each muscle sample collected from arctic ground squirrels, 67% – 76% were mapped in pairs and 75% – 85% of mapped reads were aligned to exons of the 13-lined ground squirrel genome assembly
Our study reveals a suite of transcriptional changes in genes of arctic ground squirrels that likely contribute to attenuation of muscle atrophy during the prolonged physical inactivity of hibernation
Summary
Physical inactivity generates muscle atrophy in most mammalian species. In contrast, hibernating mammals demonstrate limited muscle loss over the prolonged intervals of immobility during winter, which suggests that they have adaptive mechanisms to reduce disuse muscle atrophy. The first comparative study of transcriptional changes on a genomic scale (9,147 genes) in skeletal muscle of hibernators revealed an elevated expression of genes involved in protein biosynthesis and ribosome biogenesis pathways, but no coordinated directional changes of genes within protein catabolic pathways in arctic ground squirrels or hibernating black bears[10]. These findings are in contrast to the reduction of protein biosynthesis and elevated expression of catabolic genes that are commonly detected in atrophying muscle of traditional mammalian models of disuse[11]
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