PPAR-alpha

PPAR-alpha is a receptor inside the cell nucleus. When it is activated, it changes which genes the cell reads, including genes involved in inflammation and fat metabolism.

The evidence

• In 2005, Lo Verme and colleagues showed that palmitoylethanolamide activates PPAR-alpha in cells, with half-maximal activation at about 3 micromolar.
• In the same work, palmitoylethanolamide reduced swelling in a standard mouse model. It did not do so in mice bred without PPAR-alpha.
• Later animal studies in several models point to PPAR-alpha as the main mediator.

A 2022 mouse study, Lama 2022, reported that blocking PPAR-alpha in cell experiments removed the effects of palmitoylethanolamide.

The caveats

Rankin and Fowler 2020 call the common label “PPAR-alpha agonist” slightly misleading. Some reported effects of palmitoylethanolamide do not involve this receptor, and those other targets are not fully identified.

The evidence is from cells and laboratory animals, and almost all of the animal studies used males only.