The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
By Jesse Lo Verme, Jin Fu, G. Astarita, G. La Rana, R. Russo, A. Calignano, Daniele Piomelli. Molecular Pharmacology, 2005
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Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized mechanism. Here, we identify the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) as the molecular target responsible for the anti-inflammatory properties of PEA. PEA selectively activates PPAR-α in vitro with an EC50 value of 3.1 ± 0.4 μM and induces the expression of PPAR-α mRNA when applied topically to mouse skin. In two animal models, carrageenan-induced paw edema and phorbol ester-induced ear edema, PEA attenuates inflammation in wild-type mice but has no effect in mice deficient in PPAR-α. The natural PPAR-α agonist oleoylethanolamide (OEA) and the synthetic PPAR-α agonists GW7647 and Wy-14643 mimic these effects in a PPAR-α–dependent manner. These findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPAR-α.
Subfields: Molecular Biology, Pathology and Forensic Medicine, Pharmacology
View Paper: https://www.semanticscholar.org/paper/3d6715d1b00a9fb9cb65c3c56b67b7f4b08447a2
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Citations in the corpus
- Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications (2017, background): “…mechanism” is founded on the ability of PEA to directly stimulates either a not characterized cannabinoid CB2 receptor-like target (Calignano et al., 2001; Costa et al., 2008), or the PPAR-alpha, responsible for the regulation of the anti-inflammatory properties of PEA (Lo Verme et al., 2005).”
- International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2 (2010, background): “There is evidence that oleoyl ethanolamide has an important physiological role as a peripherally acting agent that reduces food intake (Lo Verme et al., 2005b) and this effect of oleoyl ethanolamide may be mediated, at least in part, by GPR119 (Overton et al., 2006).”
- The orphan receptor GPR55 is a novel cannabinoid receptor (2007, background): “Nevertheless, PEA has also been demonstrated to be activating antiinflammatory activities through peroxisome proliferatoractivated receptor a mediation (Lo Verme et al., 2005) and thus such contributions to an anti-inflammatory effect have to be considered.”