Horvath T L
Department of Ob/Gyn and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510-8016, USA.
Int J Obes (Lond). 2006 Apr;30 Suppl 1:S30-2. doi: 10.1038/sj.ijo.0803275.
Presentations in this symposium addressed effects and modes of action of endocannabinoids in various tissues in relation to metabolic disorders. Endocannabinoids are produced and exert their effect in various brain sites, including the mesolimbic reward circuitry and the hypothalamus. Both of these regions have direct ties to energy metabolism regulation, particularly food intake and energy expenditure. These data clearly suggest that the observed beneficial effects of CB1 (cannabinoid receptor 1) receptor antagonists on obesity may be related to the central endocannabinoid system. On the other hand, data presented on cannabinoid action in the liver and white adipose tissues clearly indicate that CB1-mediated events in affecting metabolic phenotype may occur in peripheral tissues as well. This together with the reported results from human trials on CB1 antagonists showing that the initial anorectic effect of rimonabant is diminished after the first weeks while longer lasting weight loss is achieved do indicate that peripheral action of cannabinoids are very important in body weight regulation. Should this hold true in the long run, antagonizing CB1 receptors with compound not crossing the blood-brain barrier could revolutionize pharmaceutical approaches to obesity by offering a tool that short cuts the central nervous system.
本次研讨会的报告探讨了内源性大麻素在与代谢紊乱相关的各种组织中的作用及作用方式。内源性大麻素在包括中脑边缘奖赏回路和下丘脑在内的多个脑区产生并发挥作用。这两个区域都与能量代谢调节直接相关，尤其是食物摄入和能量消耗。这些数据清楚地表明，观察到的CB1（大麻素受体1）受体拮抗剂对肥胖的有益作用可能与中枢内源性大麻素系统有关。另一方面，关于大麻素在肝脏和白色脂肪组织中作用的数据清楚地表明，CB1介导的影响代谢表型的事件也可能发生在外周组织中。这与关于CB1拮抗剂的人体试验报告结果一起表明，大麻素的外周作用在体重调节中非常重要。从长远来看，如果确实如此，使用不穿过血脑屏障的化合物拮抗CB1受体可能会通过提供一种绕过中枢神经系统的工具，彻底改变肥胖症的药物治疗方法。
