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  • Review Article
  • Published:

Motilin: from gastric motility stimulation to hunger signalling

Nature Reviews Endocrinology volume 15, pages 238–250 (2019)Cite this article

Subjects

Abstract

After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution — with the use of knockout models — sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease. Luminal stimuli, such as bitter tastants, have been identified as modulators of motilin release, with effects on hunger and food intake. The current state of knowledge and potential implications for therapy are summarized in this Review.

Key points

  • Motilin is a gastrointestinal hormone produced in the small intestine; during the fasting state, plasma levels of motilin fluctuate and induce gastric contractions to signal hunger via a cholinergic pathway.

  • The cyclic release of endogenous motilin in the fasting state is mainly regulated by duodenal acidification and bile acids.

  • Postprandially, the secretion of motilin is modulated by the presence of macronutrients and the release of other gut hormones (insulin, somatostatin, pancreatic polypeptide and secretin).

  • Exogenously administered motilin or motilin agonists accelerate gastric emptying via high-sensitivity neural receptors and low-sensitivity muscular receptors and increase lower oesophageal sphincter pressure but have no effect on colonic motility.

  • Stimulatory effects of motilin have been observed on hunger ratings, gallbladder emptying and glucose-induced insulin secretion.

  • Targeting the motilin receptor has therapeutic potential to treat hypomotility disorders, modulate hunger and affect glucose metabolism.

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Fig. 1: Main biological functions of motilin.
Fig. 2: Fluctuation of plasma levels of motilin during the different phases of the migrating motor complex.
Fig. 3: Relationship between interdigestive motility and hunger ratings.
Fig. 4: Relationship between interdigestive hunger ratings and plasma levels of hormones.

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Acknowledgements

E.D. is a postdoctoral fellow of the Fonds voor Wetenschappelijk Onderzoek (FWO).

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  1. Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium

    Eveline Deloose, Wout Verbeure, Inge Depoortere & Jan Tack

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  1. Eveline Deloose
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E.D., I.D. and J.T. researched data for the article, made a substantial contribution to discussion of content and wrote, reviewed and/or edited the manuscript before submission. W.V. wrote, reviewed and/or edited the manuscript before submission.

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Correspondence to Jan Tack.

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Deloose, E., Verbeure, W., Depoortere, I. et al. Motilin: from gastric motility stimulation to hunger signalling. Nat Rev Endocrinol 15, 238–250 (2019). https://doi.org/10.1038/s41574-019-0155-0

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