Peroxisome proliferator activator receptor alpha (PPARα) activation using free fatty acid library; fatty acids compared

Peroxisome proliferator activated receptor alpha (PPARA) is a nuclear hormone receptor, of particular interest for its impact on a number of health and wellness issues, including the circulatory system, wound healing, skin inflammatory issues and barrier function. To assess direct and limited indirect PPARA activation, a reporter assay was developed using a Gal4-PPARA Ligand Binding Domain (LBD) fusion construct and the upstream activating sequence (UAS) controlling luciferase production.

Here we describe the evaluation of a compound library containing 68 different free fatty acids, many of them are of current interest in the food and nutrition industry. Their activation of PPARA was evaluated using the Gal4-UAS PPARA reporter assay above. Many of them activated PPARA with some limitations on the size and saturation status of the individual compounds. Oleic acid and linoleic acid were two activating molecules that were selected for further analysis and evaluated side by side. They activated PPARA and this activation was blocked by a known PPARA inhibitor, GW6471 at 10 uM. Activation of specific genes involved with keratinocyte differentiation, wound repair and barrier function were evaluated and discussed.