In the beginning of the nineties the nucleic receptors, like PPAR-alpha, have been descoverd.^[1][2] The search of this receptor started, because scientists wanted to know the mechanism of action of the molecules on which they did research. These molecules could lower the lipids in blood serum, influence the fat burning, and stimulate the production ofperoxisomes.^[3][4][5] The name of the PPAR receptor originates of one of its actions: Proliferation of the Peroxisome Activated Receptor, PPAR.

Peroxisomes are vesicles in the cell, especially liver cells, containing hydrogenperoxide. The hydrogenperoxide in the vesicles breaks down toxic substances, like alcohol. PPAR's have many functions and have a nickname: sensors for stress situations.^[6] Thus molecules that influence PPAR are very interesting.

PEA influences PPAR-alpha

One of the actions of PPAR-alfa is this receptor regulates inflammation.^[7] Because clinical and laboratory studies have shown that PEA has an anit-inflammatory action, Italian researchers conducted a laboratory experiment on rats to find out whether PEA influences PPAR-alfa. In This experiment showed indeed that PEA affects PPAR-alfa.^[8] Rats without the PPAR-alfa, did not show any reduction on the evoked inflamation, after receiving PEA. This might suggest that the anti-inflamatory action of PEA is mediated through the PPAR-alfa. An other experiment with an allergic skin inflammation rat model showed that PEA is a natural substance with anti-inflammatory effects.^[9] PPAR stimulation supresses the production of INF-gamma and IL-17 through CD4+ Thelper-cells (immune cells), and the inhibition of migration of lymphocytes (white blood cells) to the place of inflammation, through inhibition of the production of chemokines(attraction molecules).^[10]

Not only does supresses PEA the inflammation mediated by PPAR-alfa, PEA also has a clear pain reducing effect in several pain models. ^[11] Influencing the genes by PPAR-alpha and supressing inflammaton takes houres, compared to the pain reduction which takes place immediately. Experiments in pain models show that the combination PEA and PPAR-alpha has a direct effect on the potasium channels of nerve cells.

PEA has a neuroprotective effect through PPAR-alpha

The neuroprotective effect of PEA has already been shown. That this mechanism is mediated by PPAR-alfa has been shown in a German laboratory study. Researchers used brain tissue to examine the effect of PEA.^[12] Blocking the PPAR-alpha receptor with a drug. blocking the receptor, eliminated the protective effect of PEA.

Also memory enhancement of PEA has been monitored in a rat model.^[13]

 David J. Kopsky, MD, October 2010

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