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1 Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA; Center for Drug Discovery, University of California, Irvine, Irvine, CA, USA
2 Department of Biological Sciences, California State University, Long Beach, CA, USA
3 Department of Zoophysiology, University of Aarhus, Aarhus, Denmark
4 Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA
5 Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA, USA
6 Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA; Center for Drug Discovery, University of California, Irvine, Irvine, CA, USA; Department of Pharmacology, University of California, Irvine, Irvine, CA, USA
* To whom correspondence should be addressed. E-mail: piomelli{at}uci.edu.
Oleoylethanolamide (OEA) is an endogenous lipid mediator that inhibits feeding in rats and mice by activating the nuclear receptor peroxisome proliferator-activated receptor-
(PPAR-
). In rodents, intestinal OEA levels increase about 3 fold upon refeeding, a response that may contribute to the induction of between-meal satiety. Here we examined whether feeding-induced OEA mobilization also occurs in Burmese pythons (Python molurus), a species of ambush-hunting snakes that consumes huge meals after months of fasting and undergoes massive feeding-dependent changes in gastrointestinal hormonal release and gut morphology. Using liquid-chromatography/mass-spectrometry (LC/MS), we measured OEA levels in the gastrointestinal tract of fasted (28 days) and fed (48h after feeding) pythons. We observed a nearly 300-fold increase in OEA levels in the small intestine of fed compared to fasted animals (322 ± 121 vs 1 ± 1 pmol/mg protein, n=3-4). In situ OEA biosynthesis was suggested by the concomitant increase of N-acyl phosphatidylethanolamine species that serve as potential biosynthetic precursors for OEA. Furthermore, we observed a concomitant increase in saturated, mono- and di-unsaturated, but not polyunsaturated fatty-acid ethanolamides (FAE) in the small intestine of fed pythons. The identification of OEA and other FAEs in the gastrointestinal tract of Python molurus suggests that this class of lipid messengers may be widespread among vertebrate groups and may represent an evolutionarily ancient means of regulating energy intake.
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