Turning Down the Heat: Role of Sarcolpin in Thermoregulation of Hibernating Arctic Ground Squirrels
Authors: Oliver Scott Ryan , Hunstiger Moriah M , Anderson Kyle J , Boswell Benjamin , Krishnan Jishnu K.S. , Rogers Jace D , Andrews Matthew T 
Published: June 2021

Hibernation in mammals is a whole‐body phenotype that involves profound reductions in metabolism and core body temperature resulting in a state of torpor. Some mammalian hibernators, such as ground squirrels, have the ability to reverse this state of hypometabolism by rewarming periodically (~every 1–4 weeks) to normothermic levels. The predominant sources of thermogenesis during these arousal periods have been shown to be brown adipose tissue (BAT) and skeletal muscle shivering. Recently, skeletal muscle non‐shivering thermogenesis has been speculated to be a significant source of heat production, which may occur via sarcolipin (SLN) uncoupling of sarcoendoplasmic reticulum (SR) calcium ATPase (SERCA)‐mediated calcium pumping. During torpor, the thermogenic contribution of BAT and skeletal muscle need to be reduced in order for hibernating mammals to maintain hypometabolic conditions. We hypothesized that skeletal muscle non‐shivering thermogenesis is a significant source of heat production and, in hibernating mammals, must be reduced during torpor. Skeletal muscle samples were taken from 2 species of ground squirrels (13‐lined and Arctic), in and out of torpor conditions, to assess fluctuations in protein expression. Preliminary results show that SLN expression is decreased during periods of torpor and significantly increase after terminal arousal from hibernation in the spring in both ground squirrel species. Furthermore, SERCA expression significantly increased during torpor in Arctic ground squirrels, which fell to normothermic levels post arousal, suggesting an enhancement of calcium handling during torpor. Next, Arctic ground squirrels were implanted with peristaltic pumps subcutaneously which delivered inhibitors of BAT‐uncoupling (SR59230A) or skeletal muscle‐uncoupling (dantrolene) during hibernation to quantify the effect of reducing specific thermogenic mechanisms directly on rewarming and metabolic rate during interbout arousals. To measure metabolic rate changes in AGS, VO2 was monitored during rewarming using respirometry. Results show that suppressing skeletal muscle uncoupling; using dantrolene (RyR inhibitor that decreases cytosolic calcium) caused a dose dependent reduction in metabolic rate during AGS rewarming. Inhibition of BAT thermogenesis resulted in faster rates of metabolism increase during IBAs. These data suggest that skeletal muscle nonshivering thermogenesis could be a significant regulator of core body temperature and basal metabolic rate, which need to be suppressed during hibernation to maintain torpor.Support or Funding InformationThirteen lined ground squirrel data funded by NIH Grant 1RC2HL101625‐01, U.S. Army Medical Research and Materiel Command contract W81XWH‐11‐0409, and the University of Minnesota McKnight Presidential Endowment. Arctic Ground Squirrel data supported by a UAF INBRE IDeA pilot award from NIH NIGMS grant number P20GM103395.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.