Molecular mechanism underlying muscle mass retention in hibernating bats: Role of periodic arousal

Abstract

Hibernators like bats show only marginal muscle atrophy during prolonged hibernation. The current study was designed to test the hypothesis that hibernators use periodic arousal to increase protein anabolism that compensates for the continuous muscle proteolysis during disuse. To test this hypothesis, we investigated the effects of 3-month hibernation (HB) and 7-day post-arousal torpor (TP) followed by re-arousal (RA) on signaling activities in the pectoral muscles of summer-active (SA) and dormant Murina leucogaster bats. The bats did not lose muscle mass relative to body mass during the HB or TP-to-RA period. For the first 30-min following arousal, the peak amplitude and frequency of electromyographic spikes increased 3.1- and 1.4-fold, respectively, indicating massive myofiber recruitment and elevated motor signaling during shivering. Immunoblot analyses of whole-tissue lysates revealed several principal outcomes: (1) for the 3-month HB, the phosphorylation levels of Akt1 (p-Akt1) and p-mTOR decreased significantly compared to SA bats, but p-FoxO1 levels remained unaltered; (2) for the TP-to-RA period, p-Akt1 and p-FoxO1 varied little, while p-mTOR showed biphasic oscillation; (3) proteolytic signals (i.e., atrogin-1, MuRF1, Skp2 and calpain-1) remained constant during the HB and TP-to-RA period. These results suggest that the resistive properties of torpid bat muscle against atrophy might be attained primarily by relatively constant proteolysis in combination with oscillatory anabolic activity (e.g., p-mTOR) corresponding to the frequency of arousals occurring throughout hibernation.

Daily torpor reduces mass and changes stress and power output of soleus and EDL muscles in the Djungarian hamster, Phodopus sungorus

“…Such arousal bouts could help to reduce the muscle disuse stimulus for both skeletal muscle atrophy and changes in mechanical properties, in keeping with recent findings that low volume exercise can reduce muscle disuse atrophy in humans (Oates et al, 2010). Arousal from torpor bouts in bats coincides with increases in protein synthesis via activation of mammalian target of rapamycin (mTOR), helping to stop or reduce muscle atrophy during hibernation (Lee et al, 2010). The amount of muscle atrophy can dramatically differ between skeletal muscles in the same species, with different molecular pathways seemingly responsible for such differences (Nowell et al, 2011).…”

Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation

“…Thus, neural activation and/or neurally related trophic factors only play a small role in retaining muscle properties during hibernation. It has been suggested that shivering is a mechanism by which hibernating bats minimize the amount of muscle atrophy (Lee et al, 2010) and could be a mechanism by which disuse atrophy is minimized in hibernating bears (Harlow et al, 2004;Lohuis et al, 2007). A more likely mechanism suggested by this study is that the signaling pathways that regulate the catabolic processes of skeletal muscle are not responsive to the mechanical and neural stimuli that normally control those pathways.…”

Mechanisms underlying inhibition of muscle disuse atrophy during aestivation in the green-striped burrowing frog, Cyclorana alboguttata

“…The absence of any increase in calpain 1 and 2 protein abundance or their autolysed forms in aestivating C. alboguttata muscle could represent a mechanism by which aestivating frogs limit proteolysis in skeletal muscle. In agreement with our study, Lee et al (Lee et al, 2010) found no difference in the protein abundance of calpain 1 in pectoralis muscles of summer-active and 3-month hibernating Murina leucogaster bats, a species which also undergoes minimal loss in muscle mass despite inactivity during dormancy. Protein levels of both calpain 1 and 2 were also recently found to be unaffected by hibernation in squirrels (Yang et al, 2014).…”

“…For example, recent studies have emphasised the importance of maintaining protein synthesis in hibernating muscle via activation of the mammalian target of rapamycin (mTOR) signalling cascade (e.g. Andres-Mateos et al, 2013;Fedorov et al, 2014;Lee et al, 2010;Nowell et al, 2011). The mTOR is a major effector of cell growth and proliferation via the regulation of protein synthesis through a multitude of downstream targets.…”

“…The mTOR is a major effector of cell growth and proliferation via the regulation of protein synthesis through a multitude of downstream targets. S. lateralis squirrels decrease myostatin expression (an mTOR inhibitor) in skeletal muscles that are resistant to winter atrophy, potentially facilitating mTOR signalling by suppressing this inhibition (Nowell et al, 2011), while periodic arousals from winter hibernation in bats appears to be associated with oscillations in the activation of mTOR (Lee et al, 2010).…”