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Gut-brain signalling describes the interaction between the gastrointestinal tract and the brain, and how secretion of varying hormones from different areas of the body causes appetite-enhancing and satiety signals to be sent to the brain. The hormones that have been most intensely studied are: ghrelin, obestatin, cholecystokinin (CCK), GLP-1, peptide YY (PYY) and insulin which all play major roles in appetite regulation. The vagus nerve is also a key mediator of regulation, and all of these inputs are processed by areas in the brain such as the hypothalamus and the nucleus tractus solitarii (NTS).

Anorexic Signals

Gut-Brain signaling Pathways Proteins and hormones activate brain pathways in different ways, either by eventual vagal activation or through peripheral circulation. The nucleus tractus solitarii and the arcuate nucleus are then activated.

Cholecystokinin (CCK) is a peptide hormone synthesised by L-cells in the mucosal epithelium of the duodenum, and secreted in response to the presence of partly digested lipids and protein]]s. CCK inhibits gastric emptying and stimulates the release of digestive enzymes from the pancreas and bile from the gall bladder by acting at CCK-A receptors (mainly found in the periphery but also found in some areas of the CNS). Because gastric emptying is inhibited, the partly digested lipids and proteins are exposed to the digestive enzymes and bile so are further broken down. As the lipids and proteins are broken down, CCK secretion declines.

CCK acts as a ‘gatekeeper’ for the response of other gut-brain signalling hormones on the afferent vagal neurons. At low levels (after fasting), CCK stimulates the expression of receptors associated with the stimulation of food intake, including receptors for melanin concentrating hormone (MCH)-1 and cannabinoid CB1 receptors. At high levels (after food consumption), MCH-1 and CB1 receptors are down- regulated. Therefore CCK, at a high or low concentration, can affect how afferent vagal neurons respond to other neurohormones.

In rats, CCK inhibits food intake in younger individuals more effectively than in older individuals. It also has a greater effect in males than in females.

Glucagon-like peptide-1 (GLP-1) is a hormone secreted from L-cells in the mucosal epithelium of the duodenum and small intestine. It is derived from the pro-glucagon gene, and is secreted into the circulation in response to the presence of nutrients. It acts at the pancreas, where it stimulates insulin secretion and suppresses glucagon secretion. It also increases insulin sensitivity. GLP-1 also activates anorexigenic neurons in the arcuate nucleus via the caudal brainstem. Activation of these neurons induces satiety and decreases food intake/hunger. It also decreases gastric emptying, so adds to the feeling of being ‘full’. At higher concentrations, GLP-1 causes nausea, and can induce conditioned taste aversion, where the brain associates the taste of a certain food with being toxic (usually after an individual consumes a food that had made them sick).

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