The role of motilin in the control of appetite and as a target for regulation of food intake

Motilin is a gut hormone produced by the duodenum that is involved in the control of gastrointestinal motility during the fasting state. Recent research has identified motilin as an orexigenic (i.e. appetite-stimulating) gut peptide. Intragastric administration of bitter agonists inhibits the release of motilin in healthy subjects and this is accompanied by a decrease in hunger and food intake. These findings establish a potential for motilin as a target for the treatment of overweight or obesity. Because motilin is not expressed in rodents, the mechanisms governing the regulation and control of secretion still remain poorly understood. The PhD project will focus on several aspects related to the function and impact of motilin. 1) To further establish the potential of bitter tastants as agents to suppress hunger and decrease food intake in overweight subjects, 2) to study the effects of GLP-1 analogs on motilin signalling, hunger ratings and food intake in healthy controls, 3) conduct research on the effect of a synthetic bile acid, obeticholic acid, on the bile acid pool, on motility, on motilin release and on the control of food intake, and 4) continue studies on the control of motilin release in duodenal cultures. The PhD candidate will interact with (bio-)medical staff and will be involved in the human studies. The candidate will take the lead in contributing the biotechnological and analytical aspects of the studies and result interpretations. With this multidisciplinary bench to bedside approach, the PhD project will take optimal advantage of previous research progress, and will benefit from the knowledge and expertise in the TARGID laboratory.