Afferent signals from the stomach play an important role in inhibition of food intake during a meal. The gastric hormone ghrelin can influence gastric satiety signalling by altering the sensitivity of gastric vagal afferents. Changes in diet, including food restriction and high fat diet (HFD) alter satiety signalling. We hypothesised that the function of gastric vagal afferent endings are affected by both a period of food restriction and a high fat diet, and that the inhibitory effect of ghrelin on vagal afferents is influenced by the different feeding conditions. We found that both fasting and HFD reduced the responses of gastric vagal tension receptors to distension, but not responses of mucosal receptors to mucosal contact. We traced vagal afferents anterogradely to their terminals in the mucosa where we found they were in close apposition to ghrelin-containing cells. Ghrelin receptor mRNA was expressed in vagal afferent cell bodies of the nodose ganglia, and increased in response to caloric restriction, but decreased in HFD mice. In control mice, ghrelin decreased the sensitivity of tension but not mucosal receptors. After caloric restriction or high fat diet, ghrelin inhibited mucosal receptors, and the inhibition of mechanosensitive tension receptors was enhanced. Therefore, both caloric restriction and HFD decrease mechanosensory vagal afferent signals, and augment the inhibitory effect of ghrelin on vagal afferents, but different mechanisms mediate the short- and longer-term changes.
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