Di Marzo V
Endocannabinoid Research Group at the Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, 80078, Pozzuoli (NA), Italy.
Diabetologia. 2008 Aug;51(8):1356-67. doi: 10.1007/s00125-008-1048-2. Epub 2008 Jun 18.
Endocannabinoids (ECs) are defined as endogenous agonists of cannabinoid receptors type 1 and 2 (CB1 and CB2). ECs, EC anabolic and catabolic enzymes and cannabinoid receptors constitute the EC signalling system. This system participates in the control of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat. Following unbalanced energy intake, however, the EC system becomes dysregulated, and in most cases overactive, in several organs participating in energy homeostasis, particularly, in intra-abdominal adipose tissue. This dysregulation might contribute to excessive visceral fat accumulation and reduced adiponectin release from this tissue, and to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. This phenomenon might form the basis of the mechanism of action of CB1 antagonists/inverse agonists, recently developed by several pharmaceutical companies as adjuvants to lifestyle modification for weight reduction, glycaemic control and dyslipidaemia in obese and type 2 diabetes patients. It also helps to explain why some of the beneficial actions of these new therapeutics appear to be partly independent from weight loss.
内源性大麻素（ECs）被定义为1型和2型大麻素受体（CB1和CB2）的内源性激动剂。内源性大麻素、内源性大麻素合成与分解代谢酶以及大麻素受体构成了内源性大麻素信号系统。该系统在多个层面参与脂质和葡萄糖代谢的调控，其可能的最终结果是能量以脂肪形式积累。然而，在能量摄入失衡后，内源性大麻素系统在参与能量稳态的多个器官中，尤其是腹部内脂肪组织中，会出现失调，且在大多数情况下会过度活跃。这种失调可能导致内脏脂肪过度积累以及该组织中脂联素释放减少，并引发与肥胖和2型糖尿病相关的多种心血管代谢风险因素。这一现象可能构成了几家制药公司最近开发的CB1拮抗剂/反向激动剂作用机制的基础，这些药物被用作肥胖和2型糖尿病患者生活方式改变的辅助药物，用于减轻体重、控制血糖和血脂异常。这也有助于解释为什么这些新疗法的一些有益作用似乎部分独立于体重减轻。
