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}
}
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… 
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756 Citations

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A novel site of action of ODA through PPAR nuclear receptors is identified and how ODA should be considered as a weak PPARγ ligand in vitro is shown.
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It is illustrated that PPARγ ability to alleviate obesity-associated inflammation raises an interesting pharmacologic potential and the protective role of PPARα and PPARβ/δ against the hepatic inflammatory response is also addressed.
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It is reported that agonists of the nuclear receptor PPAR-α (peroxisome proliferator-activated receptor-α) suppress pain behaviors induced in mice by chemical tissue injury, nerve damage, or inflammation and may represent a novel class of analgesics.
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TLDR
Central PEA administration significantly reduced the expression of the proinflammatory enzymes cyclooxygenase-2 and inducible nitric-oxide synthase, and it significantly restored carrageenan-induced PPAR-α reduction in the spinal cord, confirming the involvement of this transcriptional factor in the control of peripheral inflammation.
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The roles of PPARs in the physiopathology and therapies of the most important IBDs, ulcerative colitis (UC), and Crohn's disease (CD), as well some new experimental compounds with PPAR activity as promising drugs for IBD treatment are discussed.
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The increased inflammatory response observed in PPar‐αΚΟ mice strongly suggests that a PPAR‐α pathway modulates the degree of acute inflammation in the mice.
The role of transient receptor potential vanilloid receptor 1 and peroxisome proliferator-activated receptors-&agr; in mediating the antinociceptive effects of palmitoylethanolamine in rats
TLDR
Modulating transient receptor potential vanilloid receptor 1 activity could provide the mechanism that underlies PEA antinociceptive effects observed in vivo.
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References

SHOWING 1-10 OF 49 REFERENCES
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
TLDR
The results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders, are identified.
Oleoylethanolamide Stimulates Lipolysis by Activating the Nuclear Receptor Peroxisome Proliferator-activated Receptor α (PPAR-α)*
TLDR
The results suggest that OEA stimulates fat utilization through activation of PPAR-α and that this effect may contribute to its anti-obesity actions.
The mechanisms of action of PPARs.
TLDR
The current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases is presented.
Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation
TLDR
Findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis and inflammatory bowel disease.
Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models.
TLDR
The anti-inflammatory properties of peroxisome proliferator activated receptor-alpha agonists, coupled with their anti-proliferative and pro-differentiating effects, suggest that they could be beneficial for the treatment of a variety of cutaneous diseases.
Peroxisome proliferator-activated receptor alpha inhibits hepatic S14 gene transcription. Evidence against the peroxisome proliferator-activated receptor alpha as the mediator of polyunsaturated fatty acid regulation of s14 gene transcription.
TLDR
Find that the cis-regulatory elements for WY14643/PPARalpha and PUFA are functionally and spatially distinct argues against PPARalpha as the mediator of PUFA suppression of S14 gene transcription.
Effects of cannabinoid receptor ligands on LPS-induced pulmonary inflammation in mice.
Peroxisome proliferator-activated receptor α target genes
TLDR
The involvement of PPAR α in peroxisomal and mitochondrial fatty acid oxidation, microsomal fatty acid hydroxylation, lipoprotein, bile and amino acid metabolism, glucose homeostasis, biotransformation, inflammation control, hepato-carcinogenesis and other pathways is reviewed through a detailed analysis of the different known or putative PPARα target genes.
The palmitoylethanolamide family: a new class of anti-inflammatory agents?
TLDR
In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.
Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo‐oxygenase systems
TLDR
It is shown, for the first time, that palmitoylethanolamide has a curative effect in a model of acute inflammation, inhibiting the carrageenan‐induced oedema in a dose‐ and time‐dependent manner.
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