Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake

Provensi, Gustavo and Coccurello, Roberto and Umehara, Hayato and Munari, Leonoardo and Giacovazzo, Giacomo and Galeotti, Nicoletta and Nosi, Daniele and Gaetani, Silvana and Romano, Adele and Moles, Anna and Blandina, Patrizio and Passani, Maria Beatrice (2014) Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake. Proceedings of the National Academy of Sciences, 111 (31). pp. 11527-11532. ISSN 0027-8424

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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.

Item Type: Article
Subjects: 500 Scienze naturali e Matematica
500 Scienze naturali e Matematica > 570 Scienze della vita; Biologia
Depositing User: PhD Roberto Coccurello
Date Deposited: 21 Dec 2016 14:08
Last Modified: 21 Dec 2016 14:08

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