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An anorexic lipid mediator regulated by feeding

Nature volume 414, pages 209–212 (2001)Cite this article

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.

Author information

Author notes

  1. F. Nava

    Present address: Department of Neuroscience ‘B. B. Brodie’, University of Cagliari, Cagliari, Italy

  2. E. Murillo-Rodríguez

    Present address: Department of Physiology, Universidad Nacional Autónoma de México, Mexico City, Mexico

Authors and Affiliations

  1. Department of Psychobiology, Complutense University, Madrid, 28233, Spain

    F. Rodríguez de Fonseca, M. Navarro, R. Gómez & L. Escuredo

  2. Fundación Hospital Carlos Haya, Málaga, 29010, Spain

    F. Rodríguez de Fonseca

  3. Department of Pharmacology,

    F. Nava, J. Fu, E. Murillo-Rodríguez, A. Giuffrida, J. LoVerme, S. Gaetani, S. Kathuria & D. Piomelli

  4. Department of Anatomy and Neurobiology, University of California, Irvine, 92697, California, USA

    C. Gall

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Correspondence to D. Piomelli.

Supplementary information

Supplementary Figure 1

(GIF 11.8 KB)

Behavioral specificity of OEA-induced hypophagia. Effects of i.p. vehicle (V) or OEA (5 or 20 mg per kg) on: a, rectal temperature; b, latency to jump in the hot plate test for analgesia; c, percent time spent in open arms in the elevated plus maze test for anxiety; d, cumulative water intake; e, number of operant responses for food. Asterisk, P < 0.05; two asterisks, P < 0.01, n = 8-12 per group.

Supplementary Table 2. Effects of OEA on blood chemistry.
Full size table
Supplementary Table 3. Effects of intracerebroventricular OEA on food intake.
Full size table

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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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