N-acylethanolamines, anandamide and food intake.
Anandamide and the other N-acylethanolamines, e.g. oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA), may be formed by several enzymatic pathways from their precursors, which are the N-acylated ethanolamine phospholipids. The exact enzymatic pathways involved in their biosynthesis in specific tissues are not clarified. It has been suggested that endogenous anandamide could stimulate food intake by activation of cannabinoid receptors in the brain and/or in the intestinal tissue. On the other hand, endogenous OEA and PEA have been suggested to inhibit food intake by acting on receptors in the intestine. At present, there is no clear role for endogenous anandamide in controlling food intake via cannabinoid receptors, neither centrally nor in the gastrointestinal tract. However, OEA, PEA and perhaps also LEA may be involved in regulation of food intake by selective prolongation of feeding latency and post-meal interval. These N-acylethanolamines seem to be formed locally in the intestine, where they can activate PPARalpha located in close proximity to their site of synthesis. The rapid onset of OEA response and its reliance on an intact vagus nerve suggests that activation of PPARalpha does not result in formation of a transcription-dependent signal but must rely on an unidentified non-genomic signal that translates to activation of vagal afferents. Whether GPR119, TRPV1 and/or intestinal ceramide levels also contribute to the anorectic and weight-reducing effect of exogenous OEA is less clear. Prolonged intake of dietary fat (45 energy%) may promote over-consumption of food by decreasing the endogenous levels of OEA, PEA and LEA in the intestine.
Department of Pharmacology & Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark. hsh@farma.ku.dk
Harald S
HS
Hansen
Thi Ai
TA
Diep
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D063388:Endocannabinoids; D004983:Ethanolamines / Q000494:pharmacology*; D005223:Fats / Q000737:chemistry; D008041:Linoleic Acids / Q000494:pharmacology*; D009829:Oleic Acids / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000378:metabolism / Q000494:pharmacology*; D043882:Receptors, Cannabinoid / Q000378:metabolism
D001095:Arachidonic Acids; D004041:Dietary Fats; D063388:Endocannabinoids; D004983:Ethanolamines; D005223:Fats; D008041:Linoleic Acids; C022203:N-acylethanolamines; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; C488250:oleoylethanolamide; C109347:linoleoyl ethanolamide; C078814:anandamide