title: N-Acyl amines of docosahexaenoic acid and other n-3 polyunsatured fatty acids - from fishy endocannabinoids to potential leads.
abstract: N-3 Long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), in particular α-linolenic acid (18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n-3 LC-PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n-3 LC-PUFA-derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n-3 LC-PUFA-derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jocelijn
authors.initials: J
authors.lastname: Meijerink
authors.forename: Michiel
authors.initials: M
authors.lastname: Balvers
authors.forename: Renger
authors.initials: R
authors.lastname: Witkamp
mesh_terms: D000215:Acylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D063388:Endocannabinoids / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D019856:Ethanolamine / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D005395:Fish Oils / Q000737:chemistry; D005399:Fishes; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D043882:Receptors, Cannabinoid / Q000737:chemistry / Q000378:metabolism; D017747:Seafood / Q000032:analysis; D017962:alpha-Linolenic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D019856:Ethanolamine; D015118:Eicosapentaenoic Acid; D004298:Dopamine