Cholecystokinin pathways modulate sensations induced by gastric distension in humans

Abstract

Ingested fat releases CCK, causes gastric relaxation, delays gastric emptying, and limits meal size; however, the mechanistic link among these actions has not been established. Fatty acid release of CCK is chain-length sensitive; dodecanoic acid (C12) induces greater CCK release than decanoic acid (C10). The effect of C12 or C10 on tolerance to subsequent intragastric infusion of liquid was determined in healthy subjects, with and without the CCK1 receptor antagonist dexloxiglumide. Gastric wall relaxation after either fatty acid was assessed by graded volume distension and by barostat; gastric emptying was measured by gastric aspiration and by a [13 C]octanoic acid breath technique. C12 released more CCK (mean plasma CCK after vehicle, 4.7 Ϯ 0.8 pM; C10, 4.8 Ϯ 0.3 pM; C12, 8 Ϯ 1.2 pM; P Ͻ 0.05 C12 vs. C10 or vehicle) and reduced the volume of water (and of 5 and 25% glucose solutions) delivered at maximum tolerance compared with C10 or vehicle (volume of water tolerated after vehicle, 1,535 Ϯ 164 ml; C10, 1,335 Ϯ 160 ml; C12, 842 Ϯ 103 ml; P Ͻ 0.05 C12 vs. C10 or vehicle); this effect was abolished by dexloxiglumide. Intragastric volumes were always similar at the limit of tolerance, and, whereas gastric relaxation occurred to similar degrees after the fatty acids, its duration was longer after C12, which also induced a longer delay in half-gastric emptying [t 1/2(min) after vehicle, 53 Ϯ 2; C10, 67 Ϯ 3; C12, 88 Ϯ 7; P Ͻ 0.05 C12 vs. C10 or vehicle]. In conclusion, ingestion of a CCK-releasing fatty acid reduces the tolerated volume of liquid delivered into the stomach, primarily via a CCK1 receptormediated delay in gastric emptying. fatty acid; vagus; gastric emptying THE PRESENCE OF LIPID in the upper gastrointestinal tract modifies gastrointestinal function (23,24,34), and at least some of its effects are mediated by the peptide CCK (23, 24) that is released from small intestinal enteroendocrine cells by dietary free fatty acids with an acyl chain length of Ͼ11 carbon atoms (23). It has been proposed that CCK, released by dietary lipid, is one of the means whereby meal intake is limited (22), but there seems to be a paradox in the understanding of this effect, because CCK also relaxes the proximal stomach (24), a mechanism that has been proposed to increase rather than limit the amount of a meal consumed (31). Furthermore, in animals, there is evidence that CCK limits tolerance to a meal by delaying gastric emptying (26), but it is unknown whether the same is true in humans.In an attempt to clarify these uncertainties, we performed a series of studies in healthy volunteers: 1) to explore how endogenous CCK released in response to fatty acid modulates tolerance to liquids delivered into the stomach and 2) to determine the relationship between gastric emptying and gastric relaxation in modulating tolerance. We now provide evidence that endogenous CCK reduces the volume of a liquid that can be tolerated in the upper gastrointestinal tract via a CCK 1 receptor-mediated effect and that it does so primarily by del...

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.…”

“…Although it has been suggested that the suppressive effects of nutrients on subsequent energy intake are mediated by changes in gastrointestinal motility and gastrointestinal hormone release (19,37), the current study suggests that the stimulation of IPPWs and secretion of CCK and GLP-1 have to reach a "threshold" to result in suppression of energy intake. The motor patterns associated with infusion of C12 at 0.2 and 0.4 kcal/min are known to be associated with the slowing of gastric emptying (14), which is thought to play a role in suppressing energy intake (34).…”

“…There is some evidence that the effects of C12 are dependent on the release of CCK (19); for example, the inhibitory effects of C12 on gastric emptying and the perception of intragastric volume are attenuated by the CCK 1 receptor antagonist loxiglumide (19). The effects of fatty acids also appear to involve the activation of vagal afferents, either directly or via CCK (8,18).…”

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

“…Cholecystokinin, 17 ghrelin 18 and PYY peptide 19 levels are related to the fasting-eating cycle and to the motor function of the gastrointestinal tract. Duodenal infusion of lipids, like triglycerides 20 or fatty acids, 21 induces early satiety and causes both gastric relaxation and reduction of gastric emptying at least by the release of cholecystokinin. These relationships suggest that satiety mediated by cholecystokinin 22 and PYY 23 administration is related to motility changes of the gastrointestinal tract.…”

Newly published studies on satiety benefits of Korean pine nut oil (PinnoThin™)

“…CCK can be induced by fatty acids with a chain length of twelve carbons or longer [5,6]. Long chain poly-unsaturated fatty acids (PUFA) have been shown to produce a large increase in CCK response [6][7][8][9][10][11][12]. After ingestion of long chain PUFA, free fatty acids (FFA) are hydrolyzed in the gut lumen and CCK is secreted [13].…”