The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation
The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation
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DOI：
10.1038/ijo.2009.67
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Cristino, L.
中科院分区：
文献类型：
--
作者：
Di Marzo, V.;Ligresti, A.;Cristino, L.
内源性大麻素系统（ECS），特别是大麻素CB 1受体，其内源性激动剂（内源性大麻素anandamide和2-花生四烯酸甘油）和酶的生物合成和降解后介质正在成为关键球员在控制食物摄入量和能量平衡的各个方面。ECS参与刺激食物摄入的同源平衡（即，感知能量平衡不足和胃肠道负荷）和享乐（即，感知营养素的显着性和激励/动机价值）方面。内源性大麻素在大脑中的食欲产生作用是通过CB 1介导的对下丘脑食欲产生和厌食神经肽的刺激和抑制作用来实现的;通过对丘脑核壳中多巴胺释放的促进作用;以及通过调节脑干-十二指肠神经连接中感觉和迷走神经纤维的活性来实现的。反过来，大脑中花生四烯酸和2-花生四烯酸甘油和/或CB 1受体的水平受下丘脑中的瘦素、生长素释放肽和糖皮质激素的控制，受边缘前脑中多巴胺的控制，受脑干中胆囊收缩素和生长素释放肽的控制。ECS与能量平衡中的其他关键参与者之间的这些双向通信确保了内源性大麻素等局部介质以“空间”和“时间”协调的方式起作用，以增加食物摄入，特别是在几个小时的食物剥夺之后。然而，这种通信的改变也是在暴食症和肥胖症中ECS过度活跃的根本原因之一，这种现象为从CB 1受体拮抗剂开发抗肥胖药物提供了理论基础。国际肥胖杂志（2009）33，S18-S24; doi：10.1038/ijo.2009.67
The endocannabinoid system (ECS) and, in particular, cannabinoid CB1 receptors, their endogenous agonists (the endocannabinoids anandamide and 2-arachidonoylglycerol) and enzymes for the biosynthesis and degradation of the latter mediators are emerging as key players in the control of all aspects of food intake and energy balance. The ECS is involved in stimulating both the homoeostatic (that is, the sensing of deficient energy balance and gastrointestinal load) and the hedonic (that is, the sensing of the salience and the incentive/motivational value of nutrients) aspects of food intake. The orexigenic effects of endocannabinoids are exerted in the brain by CB1-mediated stimulatory and inhibitory effects on hypothalamic orexigenic and anorectic neuropeptides, respectively; by facilitatory actions on dopamine release in the nucleus accumbens shell; and by regulating the activity of sensory and vagal fibres in brainstem-duodenum neural connections. In turn, the levels of anandamide and 2-arachidonoylglycerol and/or CB1 receptors in the brain are under the control of leptin, ghrelin and glucocorticoids in the hypothalamus, under that of dopamine in the limbic forebrain and under that of cholecystokinin and ghrelin in the brainstem. These bi-directional communications between the ECS and other key players in energy balance ensure local mediators such as the endocannabinoids to act in a way coordinated in both 'space' and 'time' to enhance food intake, particularly after a few hours of food deprivation. Alterations of such communications are, however, also among the underlying causes of overactivity of the ECS in hyperphagia and obesity, a phenomenon that provided the rationale for the development of anti-obesity drugs from CB1 receptor antagonists. International Journal of Obesity (2009) 33, S18-S24; doi: 10.1038/ijo.2009.67