GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide

Abstract

Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions

“…Peculiarly, CLA has been shown to induce the biosynthesis of endogenous PPAR-α ligands, PEA and OEA, likely through a positive feedback mechanism where PPAR-α activation sustains its own cellular effects through ligand biosynthesis [182]. In addition to PPAR-α, PEA and OEA can activate, indirectly or directly, other receptors such as transient receptor potential vanilloid 1 (TRPV1) [183,184], which are also implicated in metabolism regulation and anti-inflammatory activity [185]. These data further extend CLA anti-neuroinflammatory actions, demonstrated in cultured astrocytes [186] and in vivo, where it has been shown that chronic dietary CLA intake reduces prostaglandin E2, decreases the activity of the endocannabinoid system, and inhibits angiogenesis in the mammalian brain [187][188][189].…”

Oral Capsaicinoid Administration Alters the Plasma Endocannabinoidome and Fecal Microbiota of Reproductive-Aged Women Living with Overweight and Obesity

“…Here we observed that CAE counteracted a time-dependent reduction in the circulating levels of NAEs observed in placebo-treated women. In particular, the treatment reversed the reduction in the levels of the anorectic and lipolysis-inducing and energy-expenditure-inducing mediator OEA, which acts via the activation of TRPV1, as well as of the pro-lipolytic peroxisome proliferator-activated receptor α (PPARα) and, possibly, the GLP-1-release stimulating GPCR, GPR119 [ 70 , 71 , 72 ], with no effect on AEA nor on the other CB1-activating mediator, 2-AG. CAE also counteracted the reduction of the levels of LEA and 2-OG, two other endogenous TRPV1 and GPR119 agonists [ 73 , 74 ], and of the anti-inflammatory NAEs, namely, DHEA and DPEA [ 74 , 75 , 76 ].…”

GPR55 Antagonist CID16020046 Protects against Atherosclerosis Development in Mice by Inhibiting Monocyte Adhesion and Mac-1 Expression

“…Therefore, a dose of 1 mg/kg seems to be optimal to achieve efficacy in vivo, which has recently been supported in an HFD-induced fatty liver model [ 25 ]. In addition, high-cholesterol diets were inadequate to activate GPR55, because lysophosphoinositols, the endogenous ligands of GPR55, are provided in an HFD but not in high-cholesterol diets [ 25 , 26 ]. Especially, levels of lysophosphatidylinositols of 18:0, 18:1, 18:2, and 18:3 were significantly increased in the liver after HFD feeding [ 25 ].…”

“…Especially, levels of lysophosphatidylinositols of 18:0, 18:1, 18:2, and 18:3 were significantly increased in the liver after HFD feeding [ 25 ]. Additionally, an HFD may provide other lipid agonists of GPR55, such as oleoylethanolamide and lysophosphatidylcholines [ 26 , 27 , 28 , 29 ].…”