Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine.
Oleoylethanolamide (OEA) is a lipid mediator that inhibits food intake by activating the nuclear receptor peroxisome proliferator-activated receptor-alpha. In the rodent small intestine OEA levels decrease during food deprivation and increase upon refeeding, suggesting that endogenous OEA may participate in the regulation of satiety. Here we show that feeding stimulates OEA mobilization in the mucosal layer of rat duodenum and jejunum but not in the serosal layer from the same intestinal segments in other sections of the gastrointestinal tract (stomach, ileum, colon) or in a broad series of internal organs and tissues (e.g. liver, brain, heart, plasma). Feeding also increases the levels of other unsaturated fatty acid ethanolamides (FAEs) (e.g. linoleoylethanolamide) without affecting those of saturated FAEs (e.g. palmitoylethanolamide). Feeding-induced OEA mobilization is accompanied by enhanced accumulation of OEA-generating N-acylphosphatidylethanolamines (NAPEs) increased activity and expression of the OEA-synthesizing enzyme NAPE-phospholipase D, and decreased activity and expression of the OEAdegrading enzyme fatty acid amide hydrolase. Immunostaining studies revealed that NAPE-phospholipase D and fatty acid amide hydrolase are expressed in intestinal enterocytes and lamina propria cells. Collectively, these results indicate that nutrient availability controls OEA mobilization in the mucosa of the proximal intestine through a concerted regulation of OEA biosynthesis and degradation.
Fu
Jin
J
Department of Pharmacology and Center for Drug Discovery, University of California, Irvine, California 92697, USA.
Astarita
Giuseppe
G
Gaetani
Silvana
S
Kim
Janet
J
Cravatt
Benjamin F
BF
Mackie
Ken
K
Piomelli
Daniele
D
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D063388:Endocannabinoids; D005508:Food Deprivation / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D006868:Hydrolysis; D007082:Ileum / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D009829:Oleic Acids / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063388:Endocannabinoids; D009829:Oleic Acids; D010739:Phospholipase D; D000099252:Fatty Acid Amide Hydrolases; C488250:oleoylethanolamide