Intestinal levels of anandamide and oleoylethanolamide in food-deprived rats are regulated through their precursors.
The anorectic lipid oleoylethanolamide and the orexigenic lipid anandamide both belong to the group of N-acylethanolamines that are generated by the enzyme N-acylphosphatidylethanolamine-hydrolyzing phospholipase D. The levels of the two bioactive lipids were investigated in rat intestines after 24 h of starvation as well as after 1 and 4 h of re-feeding. Total levels of precursor phospholipids and N-acylethanolamines were decreased upon food-deprivation whereas the level of the anandamide precursor molecule was significantly increased. The level of 2-arachidonoyl-glycerol was unchanged as was the activity of N-acyltransferase, N-acylphosphatidylethanolamine-hydrolyzing phospholipase D, and fatty acid amide hydrolase upon starvation and re-feeding. It is concluded that remodeling of the amide-linked fatty acids of N-acylphosphatidylethanolamine is responsible for the opposite effects on levels of anandamide and oleoylethanolamide in intestines of food-deprived rats and not an alternative biochemical route for anandamide synthesis. Furthermore, linoleoylethanolamide, which accounted for more than 50 mol% of the endogenous pool of N-acylethanolamines, was found not to have the same inhibitory effect on food intake, as did oleoylethanolamide following oral administration.
Department of Pharmacology and Pharmacotherapy, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, Denmark.
Gitte
G
Petersen
Camilla
C
Sørensen
Patricia C
PC
Schmid
Andreas
A
Artmann
Mads
M
Tang-Christensen
Steen H
SH
Hansen
Philip Just
PJ
Larsen
Harald H O
HH
Schmid
Harald S
HS
Hansen
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D063388:Endocannabinoids; D005508:Food Deprivation / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D009829:Oleic Acids / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley
D001095:Arachidonic Acids; D063388:Endocannabinoids; D009829:Oleic Acids; D010743:Phospholipids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; C078814:anandamide