Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility

Dose-related effects of lauric acid on antropyloroduodenal motility, gastrointestinal hormone release, appetite, and energy intake in healthy men

“…It has been established that the presence of C12 in the small intestinal lumen slows gastric emptying (16,19), stimulates isolated pyloric PWs (12), increases proximal gastric relaxation (19), suppresses antral (12,23) and duodenal motility (12), and stimulates the release of CCK (12,23) and GLP-1 (12). The current study extends these observations by demonstrating that the responses are dependent on the dose of C12 administered to the small intestine and that even very low doses of C12 have potent effects.…”

“…free fatty acid; cholecystokinin; glucagon-like peptide-1; pyloric motility STUDIES UTILIZING PHARMACOLOGICAL AGENTS, such as tetrahydrolipstatin, to inhibit fat digestion have provided evidence that the effects of fat on gastric emptying, gastrointestinal motility, gastrointestinal hormone secretion, and appetite are dependent on the presence of free fatty acids in the small intestine (4,10,11,22,27,29,33). The effects of free fatty acids on gastrointestinal function, including motility, hormone release, and energy intake (12,16,22,23), also are dependent on their acyl chain length. Hunt and Knox (16) were the first to demonstrate that fatty acids with a chain length of 12 and more carbon atoms empty from the stomach much more slowly than fatty acids containing 10 or fewer carbon atoms.…”

“…Intraduodenal C12 also stimulated the release of cholecystokinin (CCK) (12,23) and glucagon-like peptide-1 (GLP-1), whereas C10, in the dose evaluated, stimulated CCK, albeit to a lesser extent than C12, and had no effect on plasma concentrations of GLP-1 (12). Intraduodenal infusion of C18, but not C8, has been shown to inhibit energy intake in humans (22), and we recently reported (12) an inhibitory effect of intraduodenal infusion of C12, but not C10, on appetite and energy intake in healthy subjects.…”

“…It is, therefore, possible that either the concentration and/or the energy load of C12 used in our previous study (12) may have contributed to the observed effects of C12 on appetite, energy intake, and nausea by modulating gastrointestinal motility and hormone secretion. The concentration of the C12 solution (106 mM) employed in our previous study was based on that which had been infused intragastrically (100 mM) in humans without inducing nausea (23). The observation that infusion of C10 at a slightly higher (123 mM) concentration was not associated with adverse side effects also argues against the concept that the concentration of the C12 solution was responsible for the observed nausea.…”

29 Immunoglobulin-Like Domain Containing Receptor Mediates Fat-Stimulated Cholecystokinin Secretion

“…Of the food components that stimulate CCK secretion, fats are the most important. Fat-stimulated CCK release is readily apparent in humans but requires lipolysis of triglycerides to fatty acids of the chain length of dodecanoic acid [C12] or longer (9)(10)(11). In vitro, it has been shown that fatty acid aggregates (carbon chain length 10 or greater) can stimulate CCK secretion from the enteroendocrine cell line STC-1, and this release is accompanied by an increase in intracellular Ca 2+ ([Ca 2+ ] i ) (12,13).…”