The intestinal-derived hormone motilin, a peptide belonging to the ghrelin family, induces strong gastric contractions and hunger sensations. However, whether motilin regulates food intake and its association with gastric motility remains unclear. Rodents are unsuitable for animal studies of motilin function, as both the motilin and motilin-receptor genes exist only as pseudogenes in their genomes. In this study, we investigated the role of motilin on food intake by simultaneously monitoring gastric contractions and their central mechanisms in the house musk shrew (Suncus murinus), a small mammal that produces motilin. In the interdigestive state, plasma motilin concentrations were elevated during spontaneous phase III contractions of the migrating motor complex (MMC) than during phase I contractions. Food intake during spontaneous phase III contractions was higher than that during phase I contractions. Intravenous motilin administration stimulated food intake during phase I, although its effect was weaker than that of ghrelin. Motilin-induced food intake was abolished in vagotomized suncus. Additionally, motilin increased c-Fos expression in tyrosine hydroxylase (TH) neurons in the area postrema and nucleus of the solitary tract of the brain stem, as well as in activated neuropeptide Y and TH neurons in the arcuate nucleus of the hypothalamus. These results revealed that motilin stimulated feeding linked to gastric motility through the vagus nerve and activated brain regions associated with food intake. Our findings provide evidence that motilin regulates food intake, highlighting its potential as a therapeutic strategy for appetite disorders.
Keywords: food intake; gastric motility; motilin; suncus murinus; vagus nerve.