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.
