Li Hui, Kentish Stephen J, Wittert Gary A, Page Amanda J
Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Physiol Behav. 2018 Oct 1;194:466-473. doi: 10.1016/j.physbeh.2018.06.039. Epub 2018 Jun 28.
Gastric vagal afferents play an important role in the peripheral control of food intake. Apelin, a central appetite regulating hormone, is also abundantly released from the stomach. Whether apelin modulates gastric vagal afferent signalling is unknown. We aimed to determine whether apelin modulates gastric vagal afferent signalling under different states of nutrition. Female C57BL/6 mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD) for 12 weeks. An in vitro gastric vagal afferent preparation was used to determine the effect of apelin on gastric vagal afferent mechanosensitivity in SLD mice, fed ad libitum or fasted overnight, and HFD mice. To determine the signalling pathway of apelin via gastric vagal afferents, we determined the expression of apelin receptor (APJ receptor) in the gastric mucosa, the whole nodose ganglion and in gastric vagal afferent neurons innervating the stomach using retrograde tracing and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The location of apelin and APJ receptor within the gastric mucosa was determined by immunohistochemistry. Expression of apelin and APJ receptor mRNA in gastric mucosa was determined using qRT-PCR. Apelin inhibited the response of gastric mucosal vagal afferents to mucosal stroking in fasted SLD mice, but not in mice fed ad libitum a SLD or HFD. Apelin inhibited the response of gastric tension sensitive afferents to circular stretch in SLD mice fed ad libitum or fasted, an effect not observed in HFD mice. APJ receptor mRNA was detected in the gastric mucosa and whole nodose ganglion, but not specifically in gastric vagal afferents neurons. In the gastric mucosa, APJ receptor immunoreactive cells were co-localised or closely associated with apelin containing cells and co-localised with serotonin, gastrin, histamine and gastric intrinsic factor containing cells. In conclusion, apelin modulates gastric vagal afferent signalling in a nutritional status dependent manner. Further, apelin modulates gastric vagal afferents through an indirect pathway, possibly through the release of hormones/peptides from the gastric mucosa.
胃迷走传入神经在食物摄入的外周控制中起重要作用。阿片肽是一种中枢食欲调节激素，也大量从胃中释放。阿片肽是否调节胃迷走传入神经信号尚不清楚。我们旨在确定阿片肽在不同营养状态下是否调节胃迷走传入神经信号。将雌性C57BL/6小鼠喂食标准实验室饮食（SLD）或高脂饮食（HFD）12周。使用体外胃迷走传入神经制备方法，来确定阿片肽对自由进食或禁食过夜的SLD小鼠以及HFD小鼠胃迷走传入神经机械敏感性的影响。为了确定阿片肽通过胃迷走传入神经的信号通路，我们使用逆行追踪和实时定量逆转录聚合酶链反应（qRT-PCR），来确定阿片肽受体（APJ受体）在胃黏膜、整个结状神经节以及支配胃的胃迷走传入神经元中的表达。通过免疫组织化学确定阿片肽和APJ受体在胃黏膜内的位置。使用qRT-PCR确定胃黏膜中阿片肽和APJ受体mRNA的表达。阿片肽抑制禁食的SLD小鼠胃黏膜迷走传入神经对黏膜抚摸的反应，但对自由进食SLD或HFD的小鼠无此作用。阿片肽抑制自由进食或禁食的SLD小鼠胃张力敏感传入神经对环形拉伸的反应，在HFD小鼠中未观察到这种效应。在胃黏膜和整个结状神经节中检测到APJ受体mRNA，但在胃迷走传入神经元中未特异性检测到。在胃黏膜中，APJ受体免疫反应性细胞与含阿片肽的细胞共定位或紧密相关，并与含血清素、胃泌素、组胺和胃内因子的细胞共定位。总之，阿片肽以营养状态依赖性方式调节胃迷走传入神经信号。此外，阿片肽通过间接途径调节胃迷走传入神经，可能是通过胃黏膜释放激素/肽来实现。
