The role of n-3 PUFA-derived fatty acid derivatives and their oxygenated metabolites in the modulation of inflammation

Abstract Notwithstanding the ongoing debate on their full potential in health and disease, there is general consensus that n -3 PUFAs play important physiological roles. Increasing dietary n -3 PUFA intake results in increased DHA and EPA content in cell membranes as well as an increase in n -3 derived oxylipin and -endocannabinoid concentrations, like fatty acid amides and glycerol-esters. These shifts are believed to (partly) explain the pharmacological and anti-inflammatory effects of n -3 PUFAs. Recent studies discovered that n -3 PUFA-derived endocannabinoids can be further metabolized by the oxidative enzymes CYP-450, LOX and COX, similar to the n -6 derived endocannabinoids. Interestingly, these oxidized n -3 PUFA derived endocannabinoids of eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) have higher anti-inflammatory and anti-proliferative potential than their precursors. In this review, an overview of recently discovered n -3 PUFA derived endocannabinoids and their metabolites is provided. In addition, the use of chemical probes will be presented as a promising technique to study the n -3 PUFA and n -3 PUFA metabolism within the field of lipid biochemistry.