Muscle regeneration occurs in late hibernation despite continued loss of body mass

Mammalian hibernators are model systems that enable examination of naturally‐occurring extreme changes in physiology and morphology. The annual hibernation cycle is characterized by summer euthermy (tissue anabolism and accumulation of body fat reserves) and a shift to winter heterothermy (fasting and tissue catabolism). Any circannual patterns of skeletal muscle remodeling must accommodate extended inactivity during winter torpor bouts, the motor requirements of transient winter active periods, and sustained activity following spring emergence. Muscle volume in 13‐lined ground squirrels ( Ictidomys tridecemlineatus ) calculated from MRI images of upper hindlimb ( n =6 squirrels, n =10 serial scans) declined from hibernation onset, reaching a nadir in early February. This atrophy is consistent with limited activity and fasting through winter. Paradoxically, mean muscle volume rose sharply from February onward despite ongoing hibernation (inactivity and fasting), and despite continued total body mass decline until April. Correspondingly, the ratio of muscle volume to body mass was steady during winter atrophy (October–February) but increased (+70%) from February–May. Muscle remodeling appears well‐regulated in this hibernator despite vastly altered fuel and activity levels. We further examined muscle histology to determine whether remodeling can be explained by altered myofiber size or density, and undertook a 10‐state proteomics comparison to elucidate regulation of this annual cycle. Funding by National Institutes of Health.