Omega-3 Polyunsaturated N-Acylethanolamines: A Link Between Diet and Cellular Biology

The "endocannabinoidome" encompasses the dynamic network of endocannabinoid-like mediators and their often-redundant metabolic enzymes and "promiscuous" targets. Together, they constitute a versatile mechanism to fine-tune homeostasis. The relative concentration of its mediators is for an important part determined by the availability of their precursor molecules. Among these, several polyunsaturated fatty acids (PUFAs) are (-in)directly dependent on dietary supply. Fatty acid amides constitute an important subclass within the endocannabinoidome. These also include a number of conjugates of n-3 fatty acids, of which the biological activity largely remains to be elucidated. Most is known about the ethanolamides of DHA (DHEA) and EPA (EPEA). In particular, DHEA possesses anti-inflammatory properties, and studies indicate that it stimulates neurogenesis in brain. Both EPEA and DHEA induce apoptosis and are antiproliferative in certain tumor cell lines. Although these compounds bind to cannabinoid receptors, effects found thus far seem to take place via nonreceptor mechanisms mainly.