INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France ; University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France ; Neuropharmacology, Institute of Neurosciences, Université Catholique de Louvain, Av. Hippocrate 54, B1.54.10-10, 1200 Bruxelles, Belgium.
Mol Metab. 2013 Aug 9;2(4):393-404. doi: 10.1016/j.molmet.2013.08.001. eCollection 2013.
Type-1 cannabinoid (CB1) and leptin (ObR) receptors regulate metabolic and astroglial functions, but the potential links between the two systems in astrocytes were not investigated so far. Genetic and pharmacological manipulations of CB1 receptor expression and activity in cultured cortical and hypothalamic astrocytes demonstrated that cannabinoid signaling controls the levels of ObR expression. Lack of CB1 receptors also markedly impaired leptin-mediated activation of signal transducers and activators of transcription 3 and 5 (STAT3 and STAT5) in astrocytes. In particular, CB1 deletion determined a basal overactivation of STAT5, thereby leading to the downregulation of ObR expression, and leptin failed to regulate STAT5-dependent glycogen storage in the absence of CB1 receptors. These results show that CB1 receptors directly interfere with leptin signaling and its ability to regulate glycogen storage, thereby representing a novel mechanism linking endocannabinoid and leptin signaling in the regulation of brain energy storage and neuronal functions.
1 型大麻素 (CB1) 和瘦素 (ObR) 受体调节代谢和星形胶质细胞功能，但迄今为止尚未研究这两个系统在星形胶质细胞中的潜在联系。在体外培养的皮质和下丘脑星形胶质细胞中对 CB1 受体表达和活性进行遗传和药理学操作表明，大麻素信号控制 ObR 表达水平。缺乏 CB1 受体也明显损害了瘦素介导的转录因子 3 和 5（STAT3 和 STAT5）在星形胶质细胞中的激活。特别是，CB1 缺失导致 STAT5 的基础过度激活，从而导致 ObR 表达下调，并且在没有 CB1 受体的情况下，瘦素无法调节 STAT5 依赖性糖原储存。这些结果表明，CB1 受体直接干扰瘦素信号及其调节糖原储存的能力，从而代表了内源性大麻素和瘦素信号在调节脑能量储存和神经元功能中的一种新机制。
