How the gut sends signals in response to food

The ingestion of a meal triggers an impressive range of signalling mechanisms involving the activation of intrinsic and extrinsic neuronal circuits and the release of regulatory peptides, biogenic amines and lipid mediators. In the case of the enteroendocrine cells that secrete regulatory peptides and biogenic amines, recent work has identified cellular mechanisms of transduction involving G-protein coupled receptors which selectively respond to sweet or bitter tasting compounds, or to fatty acids. Primary afferent neurons of the vagus nerve provide a common target for many of the gut regulatory peptides. Stimulation of these neurons inhibits food intake and activates autonomic reflexes controlling gut function. These neurons exhibit previously unexpected plasticity in their neurochemical phenotype. In fasted rats, there is depressed expression of the peptide transmitter cocaine and amphetamine regulated transcript and the Y2 receptor and increased expression of CB1 and MCH-1 receptors, and melanin concentrating hormone. Release of endogenous cholecystokinin by refeeding reverses these changes. The neurochemical phenotype of vagal afferent neurons therefore depends on prior food intake, and these neurons provide a peripheral site for integration of information relevant to control of food intake and nutrient delivery to the small intestine.