Motilin beyond gut motility: a novel role in the regulation of adipose tissue metabolism

Abstract

MOTILIN IS A 22 AMINO ACID PEPTIDE present predominantly in endocrine cells of the duodenal mucosa, although it can also be found in the myenteric plexus and the thyroid gland, as well as in the brain, with the highest concentration detected in the hypothalamus (3). The orphan G protein-coupled receptor (GPR38) has been identified as the human motilin receptor, which is mainly found in the gastrointestinal (GI) tract in a species-dependent manner (3). Motilin is well known for its GI motor-stimulating properties. Its plasma concentration increases cyclically every 90‐120 min during the interdigestive fasting period to generate short intervals of strong peristaltic contractions from the stomach toward the duodenum and the small intestine. This pattern of peristaltic contractions is known as the phase III contraction of the migrating motor complex (8, 10). Most of the research regarding the role of motilin has focused on understanding the mechanisms undelying the motor-stimulating (prokinetic) properties of this peptide in the GI tract. This was further propelled by the observations that motilin could accelerate gastric emptying in patients with diabetic gastroparesis with important therapeutic applications for this peptide (5, 9, 11). The major interest has been to develop motilin agonists for the treatment of hypomobility disorders of the GI tract. In this context, very little is currently known about potential effects of motilin beyond its role in the regulation of GI tract motility. The article in this issue by Miegueu et al. (7) provides novel and compelling evidence that