食欲抑制依赖于大脑的组胺神经递质系统

　　意大利佛罗伦萨大学的一项研究发现，在食用饮食脂肪之后，吃饱的小鼠的食欲抑制依赖于大脑的组胺神经递质系统。相关文章发表于2014年7月21日的《PNAS》杂志上。

　　饥饿和饱食感受到体内的食物刺激和神经递质系统的相互作用的调控。例如，已知摄取饮食脂肪能够诱导化学物质油酰乙醇胺(OEA)从小肠中释放，刺激神经递质催产素的制造，并且抑制食物摄入。

　　Maria BeatrICE Passani及其同事研究了油酰乙醇胺(OEA)是否也利用已知能影响进食的组胺神经递质系统从而调控食物摄取。这组作者测量了与正常小鼠相比组胺水平低得不正常的小鼠的食物摄取与饱食的行为指标，并且观测到了对油酰乙醇胺(OEA)释放做出反应的食欲抑制的减少，正常小鼠的药物诱导的组胺释放增加了受油酰乙醇胺(OEA)诱导的食欲抑制。

　　这组作者还观察到了油酰乙醇胺(OEA)直接增加了小鼠大脑皮层区域的组胺释放，并且增加了富含制造催产素的神经元的神经元群的c-Fos基因的表达。

　　这组作者说，这些结果提示，正常的食欲抑制依赖于肠道油酰乙醇胺(OEA)与大脑的组胺系统之间的相互作用，而这种相互作用出现在下丘脑的制造催产素的神经元中。(来源：生物帮)

　　原文摘要：

Satiety factor oleoylethanolamide recruits the brainhistaminergic system to inhibit food intake

Gustavo Provensi, Roberto Coccurello, Hayato Umehara, Leonardo Munari,Giacomo Giacovazzo, Nicoletta Galeotti, Daniele Nosi, Silvana Gaetani, Adele Romano, Anna Moles,Patrizio Blandina and Maria Beatrice Passani

　　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 satietysignals, 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 theCNS 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 inthe 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.