Metabolism and thermogenesis in the hibernating arctic ground squirrel

Abstract

Arctic Ground Squirrels (AGS) tolerate up to eight months of fasting, inactivity, and large fluctuations in body mass. AGS utilize their fat stores Fat stores, which account for 25-50% of the total body mass, as a fuel source through the hibernation season to maintain a heterothermic body temperature pattern. Body temperature covers a 42°C range, requiring tight regulation to ensure survival. There are two main groupings of heat production that contribute or may contribute to temperature regulation: shivering and non-shivering thermogenesis (NST). The latter includes uncoupling protein 1 (UCP1) and sarcolipin (SLN) uncoupling of the sarcoendoplasmic reticulum calcium ATPase (SERCA). UCP1, located in the mitochondria of adipose tissue, is a futile proton cycler, while SLN and SERCA, found in muscle tissue, result in futile calcium cycling. However, the regulation and contribution of these individual metabolic pathways to full-body metabolism in AGS is unknown. We utilized three approaches to understand energy balance, metabolism, and thermoregulation in hibernating AGS: protein analysis of squirrels at discrete intervals over the hibernation season, modulation of the temperature conditions of the hibernaculum, and interruption of thermoregulatory pathways via dosing with pharmacological agents. We assessed whole animal metabolism in two ways: by tracking internal body temperature throughout the experiment and by measuring the full body respiratory gas exchange during arousal episodes. During the hibernation season, we observed suppression of muscle NST via SLN uncoupling, while UCP1 uncoupling remained upregulated until after spring terminal arousal. During arousal, lower hibernaculum temperatures increased both UCP1 and muscle NST. Interruption of thermoregulation during arousal, via low doses of the pharmaceutical agents dantrolene and SR59230A, did not change AGS’s ability to arouse but seemed to indicate compensation via intact metabolic pathways. Furthermore, in response to pharmacological intervention AGS were able to recruit white adipose as a thermogenic source under conditions of thermogenic stress. In conclusion, changes in whole animal respirometry, protein expression, and body temperature indicate a tightly regulated metabolism and biological fail-safes to ensure successful hibernation and survival in this novel animal model.