Modulation of Gene Expression in Muscle of Hibernating Arctic Ground Squirrels (Urocitellus parryii) and Attenuation of Disuse Muscle Atrophy

Abstract

Physical inactivity generates muscle atrophy in most mammalian species. In contrast, hibernating ground squirrels demonstrate limited muscle loss over the prolonged periods of immobility during winter suggesting 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 comparing hibernating ((late in a torpor and during torpor re‐entry after arousal) and summer active arctic ground squirrels using the next generation sequencing of transcriptome. Gene set enrichment analysis showed a coordinated up‐regulation of genes involved in all stages of protein biosynthesis and ribosome during hibernation at late torpor and entering torpor after arousal that suggests induction of translation in interbout arousals. Elevated proportion of down‐regulated gene involved in apoptosis as well as significant underexpression of atrogenes, upstream regulators (FOXO1, FOXO3, NFKB1A) and 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. Coordinated underexpression of multiple genes involved in muscle contraction and up‐regulation of genes in the fatty acid β oxidation pathway are consistent with low muscle loading and major role of lipids as fuel in muscle metabolism during hibernation. 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.Support or Funding InformationNIH [R21AR064995]; NIH Alaska INBRE [P20GM103395]; NIH COBRE [P20GM130443]