Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Br J Pharmacol. 2019 May;176(10):1443-1454. doi: 10.1111/bph.14175. Epub 2018 Apr 2.
This review focuses on recent findings of the physiological and pharmacological role of non-endocannabinoid N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs) in the intestine and their involvement in the gut-brain signalling. Dietary fat suppresses food intake, and much research concerns the known gut peptides, for example, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK). NAEs and 2-MAGs represent another class of local gut signals most probably involved in the regulation of food intake. We discuss the putative biosynthetic pathways and targets of NAEs in the intestine as well as their anorectic role and changes in intestinal levels depending on the dietary status. NAEs can activate the transcription factor PPARα, but studies to evaluate the role of endogenous NAEs are generally lacking. Finally, we review the role of diet-derived 2-MAGs in the secretion of anorectic gut peptides via activation of GPR119. Both PPARα and GPR119 have potential as pharmacological targets for the treatment of obesity and the former for treatment of intestinal inflammation. LINKED ARTICLES: This article is part of a themed section on 8 European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
这篇综述重点介绍了肠道中非内源性大麻素 N-酰基乙醇胺（NAEs）和 2-单酰基甘油（2-MAGs）的生理和药理学作用的最新发现，以及它们在肠道-大脑信号转导中的作用。膳食脂肪可抑制食物摄入，许多研究都集中在已知的肠道肽，例如胰高血糖素样肽-1（GLP-1）和胆囊收缩素（CCK）上。NAEs 和 2-MAGs 代表了另一类局部肠道信号，很可能参与了食物摄入的调节。我们讨论了肠道中 NAEs 的假定生物合成途径和靶点，以及它们的厌食作用和根据饮食状态的肠道水平变化。NAEs 可以激活转录因子 PPARα，但评估内源性 NAEs 作用的研究通常缺乏。最后，我们综述了饮食衍生的 2-MAGs 通过激活 GPR119 对厌食性肠道肽分泌的作用。PPARα 和 GPR119 都有可能成为治疗肥胖的药理学靶点，而前者则有可能成为治疗肠道炎症的靶点。
本文是关于大麻素研究 8 欧洲研讨会的专题部分的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
