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.
Petersen
Gitte
G
Department of Pharmacology and Pharmacotherapy, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, Denmark.
Sørensen
Camilla
C
Schmid
Patricia C
PC
Artmann
Andreas
A
Tang-Christensen
Mads
M
Hansen
Steen H
SH
Larsen
Philip Just
PJ
Schmid
Harald H O
HH
Hansen
Harald S
HS
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