Characterization of adipocyte stress response pathways during hibernation in thirteen-lined ground squirrels

To avoid the harsh conditions of winter climates, hibernating mammals undergo a systematic depression of physiological function by reducing their metabolic rate. During this process, hibernators are exposed to significant stresses (e.g., low body temperature, ischemia–reperfusion) that must be dealt with appropriately to avoid irreversible tissue damage. Consequently, we investigated the contribution of stress-responsive antioxidant enzymes, heat shock proteins, signal transduction pathways (e.g., mitogen-activated protein kinases, MAPK), and transcription factors for their role in conferring tolerance to stress in the hibernating thirteen-lined ground squirrel (Ictidomys tridecemlineatus). Using a combination of multiplex protein panels and traditional immunoblotting procedures, we have focused on these stress factors in brown adipose tissue (BAT) and white adipose tissue (WAT) over cycles of torpor-arousal since they provide the means for heat production as a result of non-shivering thermogenesis and the mobilization of critical energy reserves, respectively. We show the differential and tissue-specific regulation of stress factors including a unified upregulation of the antioxidant enzyme Thioredoxin 1 in both tissues, an upregulation of superoxide dismutase (SOD1 and SOD2) in WAT, and an increase in heat shock proteins during the transitory periods of the torpor-arousal cycle (HSP90α in BAT and HSP60 in WAT). Additionally, an upregulation of the active form of ERK1/2 and p38 in BAT and select transcription factors (e.g., CREB-1 and ELK-1) in both tissues were identified. These data provide us with greater insight into the molecular mechanisms responsible for this animal’s natural stress tolerance and outline molecular signatures which define stress resistance.