How lipid ingestion is sensed: the mechanisms underlying intestinal hormone secretion

Dietary lipids are potent stimulators of intestinal hormone secretion, which plays a central role in the regulation of digestion, appetite, glucose homeostasis, and lipid metabolism. Following digestion in the intestinal lumen, lipid-derived molecules are detected through complementary mechanisms involving lipid transporters, nutrient-sensing receptors, intracellular metabolic pathways, and bile acid signaling. These pathways couple nutrient availability to the secretion of enteroendocrine hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), ghrelin and serotonin, thereby coordinating local and systemic metabolic responses. In the small intestine, CD36 contributes to lipid uptake and sensing, while intracellular lipid processing and chylomicron formation influence hormone secretion. Bile acids facilitate lipid digestion and absorption and further regulate enteroendocrine function through receptor-mediated signaling pathways. This review examines the cellular and molecular mechanisms underlying intestinal lipid sensing, with particular emphasis on the roles of CD36, chylomicron formation, bile acid signaling, and nutrient-sensing receptors in the regulation of enteroendocrine hormone secretion.