Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine

AbstractOleoylethanolamide (OEA) is a lipid mediator that inhibits food intake by activating the nuclear receptor peroxisome proliferator-activated receptor- ? (PPAR-?). 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-acyl phosphatidylethanolamines (NAPEs), increased activity and expression of the OEA-synthesizing enzyme NAPE-phospholipase D (NAPE-PLD), and decreased activity and expression of the OEA-degrading enzyme fatty-acid amide hydrolase (FAAH). Immunostaining studies revealed that NAPE-PLD and FAAH 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.