• DOI:10.1124/MOL.104.006353
• Corpus ID: 12671741

The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide

@article{LoVerme2005TheNR,
  title={The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-$\alpha$ Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide},
  author={Jesse Lo Verme and Jin Fu and Giuseppe Astarita and G. La Rana and Roberto Russo and Antonio Calignano and Daniele Piomelli},
  journal={Molecular Pharmacology},
  year={2005},
  volume={67},
  pages={15 - 19}
}

• J. Lo Verme, Jin Fu, +4 authors D. Piomelli
• Published 1 January 2005
• Biology, Chemistry
• Molecular Pharmacology

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.