B.B. Brodie Department of Neuroscience and Center of Excellence for the Neurobiology of Addiction, University of Cagliari, Monserrato, Italy.
Curr Med Chem. 2010;17(14):1450-67. doi: 10.2174/092986710790980014.
Peroxisome proliferator-activated receptors (PPARs) have long been known as mediators of several physiological functions, among which the best characterized are lipid metabolism, energy balance and anti-inflammation. Their rather large and promiscuous ligand binding site has been recently discovered to accommodate, among a plethora of lipid molecules and metabolic intermediates, endocannabinoids and their cognate compounds, specifically belonging to the Nacylethanolamine group. In fact, oleoylethanolamide, palmitoylethanolamide and probably anandamide bind with relatively high affinity to PPARs and have now been included among their endogenous ligands. Through activation of PPARs these molecules exert a variety of physiological processes. Particularly, both long-term effects via genomic mechanisms and rapid non-genomic actions have been described, which in several instances are opposite to those evoked by activation of "classical" surface cannabinoid receptors. In this review, we describe how these effects are relevant under diverse physiological and pathophysiological circumstances, such as lipid metabolism and feeding behaviour, neuroprotection and epilepsy, circadian rhythms, addiction and cognition. A picture is emerging where nuclear receptors are involved in anorexiant, anti-inflammatory, neuroprotective, anti-epileptic, wakefulness- and cognitive-enhancing, and anti-addicting properties of endocannabinoid-like molecules. Further studies are necessary to fully understand cellular mechanisms underlying the interactions between endocannabinoids and PPARs, but also between their surface and nuclear receptors, and to exploit their potential therapeutic applications.
过氧化物酶体增殖物激活受体（PPARs）长期以来一直被认为是多种生理功能的调节剂，其中最具特征的是脂质代谢、能量平衡和抗炎作用。它们相当大且混杂的配体结合位点最近被发现可以容纳大量的脂质分子和代谢中间产物，包括内源性大麻素及其同源化合物，特别是 N-酰基乙醇胺类化合物。事实上，油酰乙醇胺、棕榈酰乙醇胺，可能还有花生四烯酸乙醇胺与 PPARs 具有相对较高的亲和力，并已被纳入其内源性配体。通过激活 PPARs，这些分子发挥多种生理作用。特别是，已经描述了通过基因组机制的长期作用和快速非基因组作用，这些作用在某些情况下与“经典”表面大麻素受体激活所引起的作用相反。在这篇综述中，我们描述了这些作用在各种生理和病理生理情况下的相关性，如脂质代谢和进食行为、神经保护和癫痫、昼夜节律、成瘾和认知。越来越多的证据表明，核受体参与了内源性大麻素样分子的厌食、抗炎、神经保护、抗癫痫、觉醒和认知增强以及抗成瘾特性。需要进一步的研究来充分了解内源性大麻素与 PPARs 之间相互作用的细胞机制，以及它们的表面和核受体之间的相互作用机制，并利用它们的潜在治疗应用。
