Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake
Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake
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DOI：
10.1038/sj.ijo.0803271
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发表时间：
2006-04-01
影响因子：
4.9
通讯作者：
Di Marzo, V
中科院分区：
文献类型：
--
作者：
Matias, I;Bisogno, T;Di Marzo, V
内源性大麻素在1995年首次被定义为“能够结合并功能性激活大麻素受体的内源性物质”。迄今为止，已经在动物组织中鉴定了两种公认的内源性大麻素，N-花生酰乙醇胺（anandamide）和2-花生酰甘油（2-AG），以及一些其他推定的配体，它们都来自长链多不饱和脂肪酸。花生四烯酸和2-AG的生物合成和代谢途径已被阐明，其中涉及的大多数酶已被克隆。我们现在知道，CB 1受体和组织浓度足以激活它们的内源性大麻素比最初想象的分布更广泛，并且在参与控制能量摄入和处理的大脑和外周器官中发现，包括下丘脑，丘脑核，脑干，迷走神经，胃肠道，脂肪组织和肝脏。内源性大麻素的生物合成和失活途径受到参与能量稳态的神经肽和激素的调节，内源性大麻素水平直接受饮食影响。内源性大麻素反过来调节参与营养摄入和加工的介质的表达和作用。这些串扰的基础上提出的内源性大麻素信号在控制食物摄入量的作用，从无脊椎动物到低等脊椎动物和哺乳动物，他们的扰动似乎有助于饮食失调的发展。
Endocannabinoids were first defined in 1995 as 'endogenous substances capable of binding to and functionally activating the cannabinoid receptors'. To date, two well-established endocannabinoids, N-arachiclonoylethanolamine (anandamide) and 2-arachiclonoylglycerol (2-AG), as well as a few other putative ligands, all derived from long-chain polyunsaturated fatty acids, have been identified in animal tissues. The biosynthetic and metabolic pathways for anandamide and 2-AG have been elucidated, and most of the enzymes therein involved have been cloned. We now know that CB1 receptors, and endocannabinoids in tissue concentrations sufficient to activate them, are more widely distributed than originally thought, and are found in brain and peripheral organs involved in the control of energy intake and processing, including the hypothalamus, nucleus accumbens, brainstem, vagus nerve, gastrointestinal tract, adipose tissue and liver. Endocannabinoid biosynthetic and inactivating pathways are under the regulation of neuropeptides and hormones involved in energy homeostasis, and endocannabinoid levels are directly affected by the diet. Endocannabinoids, in turn, regulate the expression and action of mediators involved in nutrient intake and processing. These cross-talks are at the basis of the proposed role of endocannabinoid signalling in the control of food intake, from invertebrates to lower vertebrates and mammals, and their perturbation appears to contribute to the development of eating disorders.