Transcriptional changes in muscle of hibernating arctic ground squirrels (Urocitellus parryii): implications for attenuation of disuse muscle atrophy

Abstract

AbstractPhysical 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.