title: Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake.
abstract: Key factors driving eating behavior are hunger and satiety, which are controlled by a complex interplay of central neurotransmitter systems and peripheral stimuli. The lipid-derived messenger oleoylethanolamide (OEA) is released by enterocytes in response to fat intake and indirectly signals satiety to hypothalamic nuclei. Brain histamine is released during the appetitive phase to provide a high level of arousal in anticipation of feeding, and mediates satiety. However, despite the possible functional overlap of satiety signals, it is not known whether histamine participates in OEA-induced hypophagia. Using different experimental settings and diets, we report that the anorexiant effect of OEA is significantly attenuated in mice deficient in the histamine-synthesizing enzyme histidine decarboxylase (HDC-KO) or acutely depleted of histamine via interocerebroventricular infusion of the HDC blocker α-fluoromethylhistidine (α-FMH). α-FMH abolished OEA-induced early occurrence of satiety onset while increasing histamine release in the CNS with an H3 receptor antagonist-increased hypophagia. OEA augmented histamine release in the cortex of fasted mice within a time window compatible to its anorexic effects. OEA also increased c-Fos expression in the oxytocin neurons of the paraventricular nuclei of WT but not HDC-KO mice. The density of c-Fos immunoreactive neurons in other brain regions that receive histaminergic innervation and participate in the expression of feeding behavior was comparable in OEA-treated WT and HDC-KO mice. Our results demonstrate that OEA requires the integrity of the brain histamine system to fully exert its hypophagic effect and that the oxytocin neuron-rich nuclei are the likely hypothalamic area where brain histamine influences the central effects of OEA.
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy;
authors: Gustavo
authors: G
authors: Provensi
authors: Institute of Cell Biology and Neurobiology, National Research Council/Fondazione Santa Lucia, 00143 Rome, Italy;
authors: Roberto
authors: R
authors: Coccurello
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy;
authors: Hayato
authors: H
authors: Umehara
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy;
authors: Leonardo
authors: L
authors: Munari
authors: Institute of Cell Biology and Neurobiology, National Research Council/Fondazione Santa Lucia, 00143 Rome, Italy;
authors: Giacomo
authors: G
authors: Giacovazzo
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy;
authors: Nicoletta
authors: http://orcid.org/0000-0002-1812-9844
authors: N
authors: Galeotti
authors: Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, 50134 Florence, Italy; and.
authors: Daniele
authors: D
authors: Nosi
authors: Dipartimento di Fisiologia e Farmacologia V. Erspamer, Sapienza Università di Roma, 00185 Rome, Italy.
authors: Silvana
authors: S
authors: Gaetani
authors: Dipartimento di Fisiologia e Farmacologia V. Erspamer, Sapienza Università di Roma, 00185 Rome, Italy.
authors: Adele
authors: A
authors: Romano
authors: Institute of Cell Biology and Neurobiology, National Research Council/Fondazione Santa Lucia, 00143 Rome, Italy;
authors: Anna
authors: A
authors: Moles
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy;
authors: Patrizio
authors: P
authors: Blandina
authors: Dipartimento di Neuroscienze, Psicologia, Area del Farmaco, e Salute del Bambino, Sezione di Farmacologia e Tossicologia, Università di Firenze, 50139 Florence, Italy; beatrice.passani@unifi.it.
authors: Maria Beatrice
authors: MB
authors: Passani
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D063388:Endocannabinoids; D005247:Feeding Behavior / Q000187:drug effects; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009829:Oleic Acids / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects*; D013997:Time Factors
chemical_list: D063388:Endocannabinoids; D009829:Oleic Acids; D016760:Proto-Oncogene Proteins c-fos; C488250:oleoylethanolamide; D006632:Histamine; D006640:Histidine Decarboxylase
keywords: BSS; PVN; behavioral satiety sequence; histamine receptors; paraventricular hypothalamic nuclei