Medical Faculty, Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Cannabis Cannabinoid Res. 2024 Feb;9(1):74-88. doi: 10.1089/can.2023.0194. Epub 2024 Jan 24.
Endocannabinoids and exogenous cannabinoids are potent regulators of feeding behavior and energy metabolism. Stimulating cannabinoid receptor signaling enhances appetite, particularly for energy-dense palatable foods, and promotes energy storage. To elucidate the underlying cellular mechanisms, we investigate here the potential role of astrocytic endocannabinoid 2-arachidonoylglycerol (2-AG). Astrocytes provide metabolic support for neurons and contribute to feeding regulation but the effect of astrocytic 2-AG on feeding is unknown. We generated mice lacking the 2-AG synthesizing enzyme diacylglycerol lipase alpha () in astrocytes (GLAST-Dagla KO) and investigated hedonic feeding behavior in male and female mice. Body weight and baseline water and food intake was characterized; additionally, the mice went through milk, saccharine, and sucrose preference tests in fed and fasted states. In female mice, the estrous cycle stages were identified and plasma levels of female sex hormones were measured. We found that the effects of the inducible astrocytic deletion were sex-specific. Acute milk preference was decreased in female, but not in male mice and the effect was most evident in the estrus stage of the cycle. This prompted us to investigate sex hormone profiles, which were found to be altered in GLAST-Dagla KO females. Specifically, follicle-stimulating hormone was elevated in the estrus stage, luteinizing hormone in the proestrus, and progesterone was increased in both proestrus and estrus stages of the cycle compared with controls. Astrocytic regulates acute hedonic appetite for palatable food in females and not in males, possibly owing to a deregulated female sex hormone profile. It is plausible that endocannabinoid production by astrocytes at least partly contributes to the greater susceptibility to overeating in females. This finding may also be important for understanding the effects of exogenous cannabinoids on sex hormone profiles.
内源性大麻素和外源性大麻素是调节摄食行为和能量代谢的有效物质。刺激大麻素受体信号会增强食欲，尤其是对能量密集的美味食物，促进能量储存。为了阐明潜在的细胞机制，我们在这里研究了星形胶质细胞内源性大麻素 2-花生四烯酸甘油（2-AG）的潜在作用。星形胶质细胞为神经元提供代谢支持，并有助于调节摄食，但星形胶质细胞 2-AG 对摄食的影响尚不清楚。我们生成了星形胶质细胞中缺乏 2-AG 合成酶二酰基甘油脂肪酶 α（Dagla）的小鼠（GLAST-Dagla KO），并研究了雄性和雌性小鼠的享乐性摄食行为。对体重和基础水及食物摄入量进行了特征描述；此外，还在喂食和禁食状态下对小鼠进行了牛奶、糖精和蔗糖偏好测试。鉴定了雌性小鼠的动情周期阶段，并测量了雌性性激素的血浆水平。我们发现，诱导性星形胶质细胞缺失的作用具有性别特异性。急性牛奶偏好降低了雌性小鼠，但不降低雄性小鼠，且该作用在动情期最明显。这促使我们研究性激素谱，发现 GLAST-Dagla KO 雌性小鼠的性激素谱发生了改变。具体而言，在动情期卵泡刺激素升高，在前期促黄体激素升高，在前期和动情期孕激素升高。星形胶质细胞调节雌性而不是雄性对美味食物的急性享乐性食欲，这可能是由于雌性性激素谱失调。星形胶质细胞产生的内源性大麻素至少部分导致了女性更容易暴饮暴食，这一发现可能对理解外源性大麻素对性激素谱的影响也很重要。
