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OtherAccelerated Communication

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

Jesse Lo Verme, Jin Fu, Giuseppe Astarita, Giovanna La Rana, Roberto Russo, Antonio Calignano and Daniele Piomelli
Molecular Pharmacology January 2005, 67 (1) 15-19; DOI: https://doi.org/10.1124/mol.104.006353
Jesse Lo Verme
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Jin Fu
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Giuseppe Astarita
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Giovanna La Rana
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Roberto Russo
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Antonio Calignano
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Daniele Piomelli
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Abstract

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.

  • Received August 17, 2004.
  • Accepted September 27, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 67 (1)
Molecular Pharmacology
Vol. 67, Issue 1
1 Jan 2005
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The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide

Jesse Lo Verme, Jin Fu, Giuseppe Astarita, Giovanna La Rana, Roberto Russo, Antonio Calignano and Daniele Piomelli
Molecular Pharmacology January 1, 2005, 67 (1) 15-19; DOI: https://doi.org/10.1124/mol.104.006353

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

Jesse Lo Verme, Jin Fu, Giuseppe Astarita, Giovanna La Rana, Roberto Russo, Antonio Calignano and Daniele Piomelli
Molecular Pharmacology January 1, 2005, 67 (1) 15-19; DOI: https://doi.org/10.1124/mol.104.006353
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