The endocannabinoid system: body weight and metabolic regulation.
The endocannabinoid system: body weight and metabolic regulation.
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DOI：
10.1016/s1098-3597(06)80041-4
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Jordan, Jens
中科院分区：
文献类型：
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作者：
Engeli, Stefan;Jordan, Jens
内源性大麻素系统引发多种尚未完全了解的生理功能。 1 型大麻素 (CB(1)) 受体拮抗剂是过去 8 年肥胖症 III 期研究中唯一成功的新药理治疗方法。尽管 (CB(1)) 受体的拮抗作用会急剧减少食物摄入量，但对体重减轻和代谢调节的长期影响似乎是通过刺激能量消耗以及与肝脏、骨骼肌、脂肪组织和胰腺生理学相关的外周效应来介导的。例如，在肝脏中，脂肪生成酶和脂肪酸合成被内源性大麻素上调，而在脂肪组织中，(CB(1))受体的拮抗作用增加了脂联素的分泌。一些研究表明，肥胖者内源性大麻素的形成增加，这可能是因为内源性大麻素的降解减少。尽管目前许多问题仍未得到解答，但内源性大麻素作为代谢调节剂的新兴概念有助于解释目前处于 III 期研究的 (CB(1)) 受体拮抗剂利莫那班 (SR141716) 的成功。
The endocannabinoid system elicits multiple physiologic functions that are not fully understood. Antagonism of cannabinoid type 1 (CB(1)) receptors has been the only successful new pharmacologic treatment approach in Phase III studies in obesity in the last 8 years. Whereas antagonism of (CB(1)) receptors acutely reduces food intake, the long-term effects on weight reduction and metabolic regulation appear to be mediated by stimulation of energy expenditure and by peripheral effects related to liver, skeletal muscle, adipose tissue, and pancreas physiology. For example, in the liver, lipogenic enzymes and fatty acid synthesis are upregulated by endocannabinoids, and in adipose tissue, antagonism of (CB(1)) receptors increases secretion of adiponectin. Some studies suggest that endocannabinoid formation is increased in obesity, perhaps because endocannabinoid degradation is decreased. Although many questions remain unanswered at present, the emerging concept of endocannabinoids as metabolic regulators helps to explain the success of rimonabant (SR141716), an antagonist of (CB(1)) receptors, currently in Phase III studies.