1 research outputs found
Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake
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