N-酰基乙醇胺（NAEs）包括N-棕榈酰乙醇胺（PEA）、N-油酰乙醇胺（OEA）、N-花生四烯酸乙醇胺（AEA，阿南胺）、N-二十二碳六烯酸乙醇胺（DHEA，神经元胶质细胞联结苏合物）及其氧化代谢产物，是一种脂质信使家族，在健康和疾病中有许多功能，包括炎症、焦虑和能量代谢。NAEs通过在大脑和周围激活各种G蛋白偶联受体（大麻素CB1和CB2受体、GPR55、GPR110、GPR119）、离子通道（TRPV1）和核受体（PPAR-α和PPAR-γ）发挥其信号作用。氧化NAEs的生物学角色，如前列腺酰胺、羟化阿南胺和DHEA衍生物，还很少被研究。证据表明，NAEs及其氧化代谢产物可能被异常调节或与肥胖、代谢综合征、癌症、神经炎症和肝硬化的病情严重程度有关联。在这里，我们全面回顾NAE生物合成和降解、它们通过脂氧酶、环氧酶和细胞色素P450代谢和这些信号脂质的生物学功能。我们讨论了通过抑制其降解来调节内源性NAE水平的最新发现和治疗潜力，目前正在临床评估用于神经精神疾病。我们还强调NAE生物合成抑制作为一种新兴的治疗机会，与内源性大麻素和NAE信号有关。版权所有©2022 The Authors。由Elsevier Ltd.出版。保留所有权利。

N-acylethanolamines (NAEs), including N-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), N-arachidonoylethanolamine (AEA, anandamide), N-docosahexaenoylethanolamine (DHEA, synaptamide) and their oxygenated metabolites are a lipid messenger family with numerous functions in health and disease, including inflammation, anxiety and energy metabolism. The NAEs exert their signaling role through activation of various G protein-coupled receptors (cannabinoid CB1 and CB2 receptors, GPR55, GPR110, GPR119), ion channels (TRPV1) and nuclear receptors (PPAR-α and PPAR-γ) in the brain and periphery. The biological role of the oxygenated NAEs, such as prostamides, hydroxylated anandamide and DHEA derivatives, are less studied. Evidence is accumulating that NAEs and their oxidative metabolites may be aberrantly regulated or are associated with disease severity in obesity, metabolic syndrome, cancer, neuroinflammation and liver cirrhosis. Here, we comprehensively review NAE biosynthesis and degradation, their metabolism by lipoxygenases, cyclooxygenases and cytochrome P450s and the biological functions of these signaling lipids. We discuss the latest findings and therapeutic potential of modulating endogenous NAE levels by inhibition of their degradation, which is currently under clinical evaluation for neuropsychiatric disorders. We also highlight NAE biosynthesis inhibition as an emerging topic with therapeutic opportunities in endocannabinoid and NAE signaling.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.