Hostname: page-component-745bb68f8f-b95js Total loading time: 0 Render date: 2025-01-26T02:27:43.485Z Has data issue: false hasContentIssue false
  • English
  • Français

Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide

Published online by Cambridge University Press:  09 March 2007

Patrice D. Cani ,
Maite Lasa Montoya ,
Audrey M. Neyrinck ,
Nathalie M. Delzenne  and
Didier M. Lambert
Patrice D. Cani
Affiliation:
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium
Maite Lasa Montoya
Affiliation:
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium Unité de Chimie pharmaceutique et de Radiopharmacie (73.40), Ecole de Pharmacie, Université catholique de Louvain, 73 Avenue E. Mounier, B-1200, Brussels, Belgium
Audrey M. Neyrinck
Affiliation:
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium
Nathalie M. Delzenne
Affiliation:
Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium
Didier M. Lambert*
Affiliation:
Unité de Chimie pharmaceutique et de Radiopharmacie (73.40), Ecole de Pharmacie, Université catholique de Louvain, 73 Avenue E. Mounier, B-1200, Brussels, Belgium
*
*Corresponding author: Professor D. M. Lambert, fax +32 2 764 73 63, email, lambert@cmfa.ucl.ac.be
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The CB1 cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant; SR141716A), and oleoylethanolamide (OEA) are known to reduce food consumption, by, at least partially, a peripheral regulation of feeding. The effects of systemic SR141716A or OEA (5 mg/kg) administrations on food consumption in 24 h food-deprived and fed rats were investigated. In fasted rats, SR141716A and OEA produced an inhibition in food intake measurable the first 20 min following injection. The increase in ghrelin levels observed in the vehicle-injected rats was abolished in animals receiving OEA and significantly reduced with SR141716A. Neither OEA nor SR141716A modified glucagon-like peptide-1 (7–36) amide portal levels 20 min after the administration. In fed rats, plasma ghrelin levels of SR141716A- and OEA-treated rats were 35% lower as compared with those of the vehicle-injected rats. These results show an influence of cannabinoid agents on circulating ghrelin levels and suggest that their short-term action on appetite seems to be in accordance with the control of secretion of gastrointestinal orexigenic peptides, mainly expressed in the upper part of the gastrointestinal tract.

Keywords

CannabinoidsGastrointestinal peptidesAppetiteRimonabantOleoylethanolamide
Type
Short communication
Information
British Journal of Nutrition , Volume 92 , Issue 5 , November 2004 , pp. 757 - 761
Copyright
Copyright © The Nutrition Society 2004

References

Bensaid, M, Gary-Bobo, M, Esclangon, A, Maffrand, JP, Le Fur, G, Oury-Donat, F & Soubrie, P (2003) The cannabinoid CB 1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 63, 908–914.Google Scholar
Black, SC (2004) Cannabinoid receptor antagonists and obesity. Curr Opin Investig Drugs 5, 389–394.Google ScholarPubMed
Casu, MA, Porcella, A, Ruiu, S, Saba, P, Marchese, G, Carai, MA, Reali, R, Gessa, GL & Pani, L (2003) Differential distribution of functional cannabinoid CB 1 receptors in the mouse gastroenteric tract. Eur J Pharmacol 459, 97–105.Google Scholar
Chan, JL, Bullen, J, Lee, JH, Yiannakouris, N & Mantzoros, CS (2004) Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J Clin Endocrinol Metab 89, 335–343.CrossRefGoogle ScholarPubMed
Cota, D, Marsicano, G, Lutz, B, Vicennati, V, Stalla, GK, Pasquali, R & Pagotto, U (2003 a) Endogenous cannabinoid system as a modulator of food intake. Int J Obesity 27, 289–301.CrossRefGoogle ScholarPubMed
Cota, D, Marsicano, G & Tschop, M (2003 b) The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 112, 423–431.Google Scholar
Cowley, MA, Smith, RG & Diano, S (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37, 649–661.CrossRefGoogle ScholarPubMed
Cummings, DE, Purnell, JQ, Frayo, RS, Schmidova, K, Wisse, BE & Weigle, DS (2001) A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50, 1714–1719.Google Scholar
Di Marzo, V, Goparaju, SK & Wang, L (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410, 822–825.CrossRefGoogle ScholarPubMed
Dornonville de la Cour, C, Bjorkqvist, M, Sandvik, AK, Bakke, I, Zhao, CM, Chen, D & Hakanson, R (2001) A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept 99, 141–150.CrossRefGoogle Scholar
Fu, J, Gaetani, S & Oveisi, F (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 425, 90–93.Google Scholar
Gaetani, S, Oveisi, F & Piomelli, D (2003) Modulation of meal pattern in the rat by the anorexic lipid mediator oleoylethanolamide. Neuropsychopharmacology 28, 1311–1316.CrossRefGoogle ScholarPubMed
Gomez, R, Navarro, M, Ferrer, B, Trigo, JM, Bilbao, A, Del Arco, I, Cippitelli, A, Nava, F, Piomelli, D, Rodriguez, de & Fonseca, F (2002) A peripheral mechanism for CB 1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22, 9612–9617.Google Scholar
Harrold, JA & Williams, G (2003) The cannabinoid system: a role in both the homeostatic and hedonic control of eating?. Br J Nutr 90, 729–734.CrossRefGoogle ScholarPubMed
Hilairet, S, Bouaboula, M, Carriere, D, Le Fur, G & Casellas, P (2003) Hypersensitization of the orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716. J Biol Chem 278, 23731–23737.Google Scholar
Jonsson, KO, Vandervoorde, S, Lambert, DM, Tiger, G & Fowler, CJ (2001) Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide. Br J Pharmacol 133, 1263–1275.CrossRefGoogle ScholarPubMed
Kirkham, TC & Williams, CM (2001) Endogenous cannabinoids and appetite. Nutr Res Rev 14, 65–86.CrossRefGoogle ScholarPubMed
Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H & Kangawa, K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660.Google Scholar
Konturek, SJ, Konturek, JW, Pawlik, T & Brzozowski, T (2004) Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol 55, 137–154.Google ScholarPubMed
Lambert, DM, DiPaolo, FG, Sonveaux, P, Kanyonoyo, M, Govaerts, SJ, Hermans, E, Bueb, J, Delzenne, NM & Tschirhart, EJ (1999) Analogues and homologues of N-palmitoylethanolamide, a putative endogenous CB(2) cannabinoid, as potential ligands for the cannabinoid receptors. Biochim Biophys Acta 1440, 266–274.Google Scholar
Lambert, DM, Vandevoorde, S, Jonsson, KO & Fowler, CJ (2002) The palmitoylethanolamide family: a new class of anti-inflammatory agents?. Curr Med Chem 9, 663–674.Google Scholar
Meier, JJ, Gallwitz, B, Schmidt, WE & Nauck, MA (2002) Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 440, 269–279.Google Scholar
Mokdad, AH, Serdula, MK, Dietz, WH, Bowman, BA, Marks, JS & Koplan, JP (2000) The continuing epidemic of obesity in the United States. JAMA 284, 1650–1651.Google Scholar
Rodriguez, de, Fonseca, F, Navarro, M & Gomez, R (2001) An anorexic lipid mediator regulated by feeding. Nature 414, 209–212.CrossRefGoogle Scholar
Thorens, B & Waeber, G (1993) Glucagon-like peptide-1 and the control of insulin secretion in the normal state and in NIDDM. Diabetes 42, 1219–1225.CrossRefGoogle ScholarPubMed
Tschop, M, Smiley, DL & Heiman, ML (2000) Ghrelin induces adiposity in rodents. Nature 407, 908–913.CrossRefGoogle ScholarPubMed