An anorexic lipid mediator regulated by feeding

Abstract

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling1. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown2. Here we show that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding.

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Figure 1: OEA suppresses food intake in rats deprived of food for 24 h.
Figure 2: Effects of subchronic OEA administration on food intake and body mass.
Figure 3: Role of peripheral sensory fibres in OEA-induced hypophagia.
Figure 4: OEA increases c-fos mRNA expression in brain regions associated with feeding behaviour.
Figure 5: Feeding regulates OEA biosynthesis in small intestine.

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Acknowledgements

We thank M. Schwartz for comments; R. Carrera and A. M. Basso for help with initial experiments; T. Dinh, M. Guzmán and C. Sánchez for reading the manuscript critically; M. A. Gorriti, J. Muñoz, F. Désarnaud, M. A. Villanúa and Y. Xie for help with experiments; and F. Valiño for editorial assistance. This research was supported by grants from the National Institute of Drug Abuse (to D.P.) and from the National Institute of Mental Health (to C.G.). Additional support was from the Comunidad de Madrid, Del Amo Program and Plan Nacional sobre Drogas (to F.R.F. and M.N.). F.R.F. is a research fellow of the Jaime del Amo Program, Complutense University.

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Correspondence to D. Piomelli.

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Rodríguez de Fonseca, F., Navarro, M., Gómez, R. et al. An anorexic lipid mediator regulated by feeding. Nature 414, 209–212 (2001). https://doi.org/10.1038/35102582

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