Fatty acid chain length determines cholecystokinin secretion and effect onhuman gastric motility

Background & Aims: Fatty acids induce cholecystokinin (CCK) secretion and m odify gastric motility, but the chain length requirements for these effects are not known. Nor is it clear whether the effects of fatty acids on gastr ic motility in humans are CCK mediated or directly exerted. The aim of this study was to determine the role of fatty acyl chain length in CCK secretio n and in influencing gastric motility. Methods: Fatty acids were infused in to the upper gut in healthy volunteers; plasma CCK was determined by radioi mmunoassay. Effects of fatty acids on antral contractility were determined by percutaneous ultrasonography; effects on proximal gastric tone were stud ied during fundal distention. Results: Plasma CCK concentration was consist ently and similarly elevated by fatty acids with a chain of 12 carbon atoms or longer, whereas those of 11 or fewer carbon atoms failed to increase pl asma CCK. A 12-carbon but not a 10-carbon-long chain fatty acid reduced ant ral contractile amplitude, an effect that was abolished by loxiglumide (a s pecific CCK-A receptor antagonist). The 12-carbon fatty acid also reduced p roximal gastric tone more than the 10-carbon fatty acid. Conclusions: A hig hly specific, chain length-sensitive fatty acid recognition system exists i n the proximal gut mediating CCK secretion and gastric motility. An additio nal, probably CCK-independent, effect of fatty acid also regulates proximal gastric tone.