What role do gut hormones play in obesity?

The term “gut-brain axis” refers to the bidirectional communication system between the gastrointestinal system and the brain. For example, the gastrointestinal tract secretes various hormones to signal the brain to regulate food (energy) intake. The most-studied gut hormones include ghrelin, glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and oxyntomodulin.

Ghrelin, secreted by the intestines, increases food intake and gastric motility; in obesity, its secretion is abnormal, and bariatric surgery seems to reduce its secretion after eating. GLP-1, secreted by the intestines, reduces appetite, slows gastric emptying, and suppresses glucagon secretion. Postmeal GLP-1 levels are reduced in people with obesity, and bariatric surgery seems to correct the reduction. In fact, GLP-1 agonists are a medication class that mimics this hormone, and they are used therapeutically for obesity. CKK, secreted by the duodenum, reduces appetite and slows gastric motility. In obesity CKK’s effects on the appetite are blunted, and these effects seem to normalize after bariatric surgery.

PP, secreted by the pancreas, seems to be able to both decrease and increase appetite, depending on where it exerts its effect. PP is structurally related to PYY, which is secreted by the intestines and decreases appetite and gut motility. PYY secretion was found to be reduced in people with obesity, and it increased after bariatric surgery. Oxyntomodulin, secreted by the intestines, reduces food intake and gastric motility. It acts on similar receptors as GLP-1 but produces a smaller incretin effect (the release of insulin in response to increased glucose in the blood). Since the incretin effect regulates blood glucose, there is interest in using oxyntomodulin to treat obesity in people without diabetes, who do not need help regulating blood glucose.^[1][2]