The gastrointestinal (GI) system plays a crucial role in regulating food intake through the release of satiation peptides, which help terminate meals and limit their size. These peptides are produced by enteroendocrine cells in the stomach, small intestine, and colon, and they act on both neural and hormonal pathways to modulate appetite. Key satiation peptides include cholecystokinin (CCK), glucagon-like peptide-1 (GLP1), oxyntomodulin, pancreatic polypeptide (PP), and amylin. CCK, produced primarily in the duodenum and jejunum, is a potent inhibitor of gastric emptying and reduces food intake when administered peripherally. GLP1, secreted mainly by L cells in the distal small intestine and colon, delays gastric emptying and inhibits glucagon secretion, leading to reduced food intake. Oxyntomodulin, also produced by L cells, decreases food intake and body weight in animals. PP, secreted by specialized islet cells, influences biliary and exocrine pancreatic function and gastric acid secretion. Amylin, co-secreted with insulin, inhibits gastric emptying and gastric acid secretion. Ghrelin, an orexigenic hormone produced by the stomach and proximal small intestine, increases food intake and is regulated by hormonal and neural signals. The mechanisms by which food triggers the release of these satiation peptides involve nutrient sensing and signal transduction pathways, including glucose uptake, intracellular metabolism, and taste-like pathways. Long-acting adiposity hormones like leptin and insulin also influence the sensitivity to short-acting satiation signals, enhancing their anorectic effects. Understanding these complex regulatory mechanisms provides promising targets for developing new strategies to combat obesity and diabetes.The gastrointestinal (GI) system plays a crucial role in regulating food intake through the release of satiation peptides, which help terminate meals and limit their size. These peptides are produced by enteroendocrine cells in the stomach, small intestine, and colon, and they act on both neural and hormonal pathways to modulate appetite. Key satiation peptides include cholecystokinin (CCK), glucagon-like peptide-1 (GLP1), oxyntomodulin, pancreatic polypeptide (PP), and amylin. CCK, produced primarily in the duodenum and jejunum, is a potent inhibitor of gastric emptying and reduces food intake when administered peripherally. GLP1, secreted mainly by L cells in the distal small intestine and colon, delays gastric emptying and inhibits glucagon secretion, leading to reduced food intake. Oxyntomodulin, also produced by L cells, decreases food intake and body weight in animals. PP, secreted by specialized islet cells, influences biliary and exocrine pancreatic function and gastric acid secretion. Amylin, co-secreted with insulin, inhibits gastric emptying and gastric acid secretion. Ghrelin, an orexigenic hormone produced by the stomach and proximal small intestine, increases food intake and is regulated by hormonal and neural signals. The mechanisms by which food triggers the release of these satiation peptides involve nutrient sensing and signal transduction pathways, including glucose uptake, intracellular metabolism, and taste-like pathways. Long-acting adiposity hormones like leptin and insulin also influence the sensitivity to short-acting satiation signals, enhancing their anorectic effects. Understanding these complex regulatory mechanisms provides promising targets for developing new strategies to combat obesity and diabetes.