INSERM U862, Avenir group Energy Balance and Obesity, Bordeaux, France.
J Psychopharmacol. 2012 Jan;26(1):114-24. doi: 10.1177/0269881111408458. Epub 2011 Aug 8.
Animal and human studies carried out so far have established a role for the endocannabinoid system (ECS) in the regulation of energy balance. Here we critically discuss the role of the endocannabinoid signalling in brain structures, such as the hypothalamus and reward-related areas, and its interaction with neurotransmitter and neuropeptide systems involved in the regulation of food intake and body weight. The ECS has been found to interact with peripheral signals, like leptin, insulin, ghrelin and satiety hormones and the resulting effects on both central and peripheral mechanisms affecting energy balance and adiposity will be described. Furthermore, ECS dysregulation has been associated with the development of dyslipidemia, glucose intolerance and obesity; phenomena that are often accompanied by a plethora of neuroendocrine alterations which might play a causal role in determining ECS dysregulation. Despite the withdrawal of the first generation of cannabinoid type 1 receptor (CB1) antagonists from the pharmaceutical market due to the occurrence of psychiatric adverse events, new evidence suggests that peripherally restricted CB1 antagonists might be efficacious for the treatment of obesity and its associated metabolic disorders. Thus, a perspective on new promising strategies to selectively target the ECS in the context of energy balance regulation is given.
迄今为止，动物和人体研究已经确定了内源性大麻素系统 (ECS) 在调节能量平衡中的作用。在这里，我们批判性地讨论了内源性大麻素信号在大脑结构（如下丘脑和与奖赏相关的区域）中的作用，以及它与参与调节食物摄入和体重的神经递质和神经肽系统的相互作用。已经发现 ECS 与外周信号（如瘦素、胰岛素、胃饥饿素和饱腹感激素）相互作用，并且将描述对影响能量平衡和肥胖的中枢和外周机制的影响。此外，ECS 失调与血脂异常、葡萄糖不耐受和肥胖的发展有关；这些现象通常伴随着大量的神经内分泌改变，这些改变可能在确定 ECS 失调方面起着因果作用。尽管由于出现精神不良事件，第一代大麻素 1 型受体 (CB1) 拮抗剂已从医药市场撤出，但新的证据表明，外周受限的 CB1 拮抗剂可能对肥胖及其相关代谢紊乱的治疗有效。因此，对内源性大麻素系统在能量平衡调节方面的新的有前途的选择性靶向策略进行了展望。
