Matias I, Bisogno T, Di Marzo V
Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.
Int J Obes (Lond). 2006 Apr;30 Suppl 1:S7-S12. doi: 10.1038/sj.ijo.0803271.
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-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (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.
内源性大麻素于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，在动物组织中已鉴定出两种公认的内源性大麻素，即N-花生四烯酰乙醇胺（花生四烯酸乙醇胺）和2-花生四烯酸甘油酯（2-AG），以及其他一些可能的配体，它们均来源于长链多不饱和脂肪酸。花生四烯酸乙醇胺和2-AG的生物合成及代谢途径已得到阐明，其中涉及的大多数酶也已被克隆。我们现在知道，CB1受体以及组织浓度足以激活它们的内源性大麻素，其分布比最初认为的更为广泛，存在于参与能量摄入和处理控制的脑和外周器官中，包括下丘脑、伏隔核、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。反过来，内源性大麻素调节参与营养物质摄入和处理的介质的表达和作用。这些相互作用是内源性大麻素信号在从无脊椎动物到低等脊椎动物和哺乳动物的食物摄入控制中所起作用的基础，而它们的紊乱似乎导致了饮食失调的发展。
