Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Leibniz Institute for Resilience Research (LIR), Mainz, Germany.
Neuropsychopharmacology. 2021 Apr;46(5):982-991. doi: 10.1038/s41386-021-00957-z. Epub 2021 Feb 8.
Palatable food can promote overfeeding beyond homeostatic requirements, thereby constituting a major risk to obesity. Here, the lack of cannabinoid type 1 receptor (CB1) in dorsal telencephalic glutamatergic neurons (Glu-CB1-KO) abrogated the overconsumption of palatable food and the development of obesity. On low-fat diet, no genotype differences were observed. However, under palatable food conditions, Glu-CB1-KO mice showed decreased body weight and food intake. Notably, Glu-CB1-KO mice were protected from alterations in the reward system after high-fat diet feeding. Interestingly, obese wild-type mice showed a superior olfactory detection as compared to mutant mice, suggesting a link between overconsumption of palatable food and olfactory function. Reconstitution of CB1 expression in olfactory cortex in high-fat diet-fed Glu-CB1-KO mice using viral gene delivery partially reversed the lean phenotype concomitantly with improved odor perception. These findings indicate that CB1 in cortical glutamatergic neurons regulates hedonic feeding, whereby a critical role of the olfactory cortex was uncovered as an underlying mechanism.
可口的食物可以促进超过稳态需求的过度喂养，从而成为肥胖的主要风险因素。在这里，背侧端脑谷氨酸能神经元（Glu-CB1-KO）中缺乏大麻素 1 型受体（CB1）消除了对美味食物的过度消耗和肥胖的发展。在低脂饮食下，没有观察到基因型差异。然而，在美味食物条件下，Glu-CB1-KO 小鼠的体重和食物摄入量减少。值得注意的是，Glu-CB1-KO 小鼠在高脂肪饮食喂养后对奖励系统的改变有保护作用。有趣的是，肥胖的野生型小鼠的嗅觉检测能力优于突变型小鼠，这表明过度食用美味食物与嗅觉功能之间存在联系。使用病毒基因传递在高脂肪饮食喂养的 Glu-CB1-KO 小鼠中重建嗅觉皮层中的 CB1 表达，部分逆转了瘦表型，同时改善了嗅觉感知。这些发现表明，皮质谷氨酸能神经元中的 CB1 调节享乐性喂养，揭示了嗅觉皮层的关键作用作为潜在机制。
