ABSTRACT
Title
Oleoylethanolamide: a new player in the “gut-brain axis” controlling food intake
Authors
S. Gaetani and V. Cuomo
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome. P.le A. Moro 5 – 00185 Rome, Italy
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome. P.le A. Moro 5 – 00185 Rome, Italy
Abstract
The spread of “obesity epidemic” and the poor efficacy of many anti-obesity therapies highlight the need to identify novel mechanisms controlling feeding and energy balance. One such mechanism involves oleoylethanolamide (OEA), the monounsatured analogue of the endocannabinoid anandamide. OEA is one of the N-acylethanolamides (NAEs) present in all living organisms that are synthesized from the precursors N-acylphosphatidylethanolamines (NAPEs), through the actions of the enzymes N-acyltransferase and NAPE-phospholipase D (NAPE-PLD), and hydrolyzed intracellularly by fatty-acid-amide hydrolase enzymes. OEA has no affinity for cannabinoid receptors nor it induces cannabimimetic effects and its biological role remained elusive for long. During the last decade it has clearly emerged that OEA is a gut-derived satiety factor controlling appetite and energy balance1. OEA is released by small-intestinal enterocytes during the absorption of dietary fat and inhibits feeding by engaging the nuclear receptor, peroxisome proliferator-activated receptor-a(PPAR-a). Previous studies have shown that the anorexic effects of systemically administered OEA require the presence of intact sensory afferents of the vagus nerve and are accompanied by the activation of c-fos expression in selected areas of the central nervous system, such as the nucleus of the solitary tract (NTS), the paraventricular nucleus (PVN) and the supraoptic nucleus (SON).
Recent evidences from in situ hybridization and immunohistochemistry experiments in rats and mice, show that systemic injections of OEA (5–10 mg kg1, intraperitoneal) enhance expression of the neuropeptide oxytocin in magnocellular neurons of the PVN and SON2. No such effect is observed with other hypothalamic neuropeptides, including vasopressin, thyrotropin-releasing hormone and pro-opiomelanocortin. The increase in oxytocin expression elicited by OEA was absent in mutant PPAR-a-null mice. Pharmacological blockade of oxytocin receptors in the brain by intracerebroventricular infusion of the selective oxytocin antagonist, L-368,899, prevented the anorexic effects of OEA, without affecting the increase of c-fos mRNA in the NTS. The results suggest that OEA suppresses feeding by activating central oxytocin transmission.
References:
1) Dipasquale P/Romano A, et al.Oleoylethanolamide: a new player in energy metabolism control. Role in food intake Drug Discovery Today: Disease Mechanisms, 2011 in press
2) Gaetani S, et al. The fat-induced satiety factor OEA suppresses feeding through central release of oxytocin. Journal of Neuroscience 2010 30(24):8096-101
Recent evidences from in situ hybridization and immunohistochemistry experiments in rats and mice, show that systemic injections of OEA (5–10 mg kg1, intraperitoneal) enhance expression of the neuropeptide oxytocin in magnocellular neurons of the PVN and SON2. No such effect is observed with other hypothalamic neuropeptides, including vasopressin, thyrotropin-releasing hormone and pro-opiomelanocortin. The increase in oxytocin expression elicited by OEA was absent in mutant PPAR-a-null mice. Pharmacological blockade of oxytocin receptors in the brain by intracerebroventricular infusion of the selective oxytocin antagonist, L-368,899, prevented the anorexic effects of OEA, without affecting the increase of c-fos mRNA in the NTS. The results suggest that OEA suppresses feeding by activating central oxytocin transmission.
References:
1) Dipasquale P/Romano A, et al.Oleoylethanolamide: a new player in energy metabolism control. Role in food intake Drug Discovery Today: Disease Mechanisms, 2011 in press
2) Gaetani S, et al. The fat-induced satiety factor OEA suppresses feeding through central release of oxytocin. Journal of Neuroscience 2010 30(24):8096-101