Specific shifts in the endocannabinoid system in hibernating brown bears

Abstract

In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. We hypothesized that specific changes should occur in hibernating brown bears ( Ursus arctos ) due to specific features, including hibernation during half the year at only mild hypothermia while remaining physically inactive without drinking or eating, and the absence of arousal episodes although bears remain sensitive to external disturbances. We explored circulating lipids and the ECS in plasma and metabolically active tissues (muscle and adipose tissue), in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid and a decrease in arachidonic acid. In adipose and muscle tissues of hibernating bears, we found lower concentrations of both two major ligands for endocannabinoid receptors, 2-arachidonoylglycerol (2-AG) and anandamide (AEA). Gene expression was reduced for enzymes that synthesize endocannabinoid compounds, whereas an increase was observed for catabolic enzymes. Reduction in ECS tone may promote mobilization of fat stores and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the maintenance of torpor (reduction in locomotion), while promoting the capacity of bears to sense stimuli from the environment.