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. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear’s peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues 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 C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level 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 conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.

中文翻译：

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棕熊冬眠时内源性大麻素系统的特定变化

在小型冬眠者中，据报道，参与调节神经元信号，进食行为，能量代谢和昼夜节律的内源性大麻素系统（ECS）的整体下调可能促使生理适应冬眠状态。在冬眠棕熊（Ursus arctos）中，我们假设，除了对ECS的整体抑制以外，内源性大麻素化合物的季节性变化可能与熊的特殊特征有关，包括冬眠而没有唤醒事件和对外部干扰做出反应的能力。当活动和冬眠时，我们在自由活动的亚成年斯堪的纳维亚棕熊中探索了血清中的循环脂质以及血浆和代谢活性组织中的ECS。在冬季熊血清中，除了总脂肪酸浓度增加了2倍外，我们发现循环脂肪酸的相对比例发生了显着变化，例如二十二碳六烯酸C22：6 n-3增加了2倍，花生四烯酸C20：4 n-6减少了。在冬眠的熊的脂肪和肌肉组织中，我们发现2-花生四烯酸甘油酯（2-AG）是大麻素受体1（CB1）和2（CB2）的主要配体，其浓度明显较低。在冬季肌肉和脂肪组织中也分别发现了编码CB1和CB2的基因的mRNA水平较低。观察到的ECS音调降低可能促进了人体脂肪储存中的脂肪酸动员，并促进了冬眠熊骨骼肌中的碳水化合物代谢。另外，冬季类似内源性大麻素的化合物N-油酰基乙醇酰胺（OEA）的高循环水平可能有助于周围组织的脂解作用和脂肪酸氧化。