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Inhibitory effect of the anorexic compound oleoylethanolamide on gastric emptying in control and overweight mice

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Abstract

Gastric emptying regulates food intake. Oleoylethanolamide (OEA), an endogenous acylethanolamide chemically related to the endocannabinoid anandamide, inhibits food intake, but its effect on gastric emptying is unknown. Here, we investigated the effect and the role of OEA on gastric emptying in mice fed either a standard (STD) or a high-fat diet (HFD) for 14 weeks. Gastric emptying was reduced by OEA, but not by its saturated analog, palmitoylethanolamide. The effect of OEA was unaffected by rimonabant (cannabinoid CB1 receptor antagonist), SR144528 (cannabinoid CB2 receptor antagonist), 5′-iodoresiniferatoxin (transient receptor potential vanilloid type 1 antagonist), or MK886 (peroxisome proliferator-activated receptor-α) antagonist. Compared to STD mice, HFD mice showed delayed gastric emptying and higher levels of gastric OEA. HFD-induced increase in OEA levels was accompanied by increased expression of the OEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-selective phospholipase D and decreased expression of the OEA-degrading enzyme fatty acid amide hydrolase. These results might suggest that elevation of gastric OEA could possibly contribute to the delayed gastric emptying observed in HFD-fed animals. HFD regulates OEA levels in the stomach through an increase of its biosynthesis and a decrease of its enzymatic degradation. The inhibitory effect of OEA on gastric emptying here observed might underlie part of the anorexic effects of this compound previously reported.

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Abbreviations

AA-5-HT:

N-arachidonoylserotonin

2-AG:

2-arachidonoylglycerol

DMSO:

Dimethylsulfoxide

FAAH:

Fatty acid amide hydrolase

HFD:

High-fat diet

OEA:

Oleoylethanolamide

I-RTX:

5′-iodoresiniferatoxin

NAPE-PLD:

N-acyl-phosphatidylethanolamine-selective phospholipase D

PEA:

Palmitoylethanolamide

PPAR:

Peroxisome proliferator-activated receptor

RT-PCR:

Reverse-transcription polymerase chain reaction

TRPV1:

Transient receptor potential vanilloid type-1

STD:

Standard diet

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Acknowledgements

This work was supported by Prin, Regione Campania, “Fondazione Enrico ed Enrica Sovena,” Epitech, S.r.l. (to SP and VDM), and Sanofi-Aventis (to VDM).

Competing interests

The authors declare no competing interests.

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Authors and Affiliations

  1. Endocannabinoid Research Group, Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy

    Gabriella Aviello, Raffaele Capasso, Francesca Borrelli, Barbara Romano, Francesco Capasso & Angelo A. Izzo

  2. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy

    Isabel Matias, Stefania Petrosino & Vincenzo Di Marzo

  3. Endocannabinoid Research Group, Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy

    Stefania Petrosino

  4. Endocannabinoid Research Group, Institute of Protein Biochemistry, National Research Council, Naples, Italy

    Pierangelo Orlando

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  1. Gabriella Aviello
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  2. Isabel Matias
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  7. Barbara Romano
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  8. Francesco Capasso
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Correspondence to Vincenzo Di Marzo or Angelo A. Izzo.

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Aviello, G., Matias, I., Capasso, R. et al. Inhibitory effect of the anorexic compound oleoylethanolamide on gastric emptying in control and overweight mice. J Mol Med 86, 413–422 (2008). https://doi.org/10.1007/s00109-008-0305-7

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  • DOI: https://doi.org/10.1007/s00109-008-0305-7

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