Role of lipase in the regulation of upper gastrointestinal function in humans

Abstract

The role of lipase in the regulation of upper gastrointestinal function is poorly understood. We studied the effect of orlistat, a new, potent, and highly specific lipase inhibitor, on gastric emptying, cholecystokinin (CCK) release, and pancreaticobiliary secretion. Three groups of studies were performed in nine healthy volunteers, using the double-indicator technique with a triple-lumen duodenal tube, polyethylene glycol 4000 as a duodenal perfusion marker, and 99mTc-diethylenetriamine pentaacetic acid as a meal marker. Gastric emptying, pancreaticobiliary output, and postprandial plasma CCK levels were measured after ingestion of the following isocaloric 500-ml liquid meals with or without 200 mg orlistat: 1) a pure fat meal (10% Intralipid), 2) a meal containing free fatty acids, or 3) an albumin-glucose meal. All experiments were performed in a randomized, placebo-controlled, crossover design. Orlistat markedly inhibited lipase activity in all three experiments. Orlistat given with the fat meal reduced CCK release and output of lipase, trypsin, and bilirubin and accelerated the rate of gastric emptying (P < 0.05). After ingestion of the free fatty acid or albumin-glucose meal, orlistat had no significant effect on any of these parameters. We conclude that lipase plays an important, nutrient-specific role in the regulation of gastric emptying and pancreaticobiliary secretion after ingestion of fatty meals in humans.

Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats†

“…Guerciolini 41 reported no significant effects of Orl on intestinal transit time or gastric emptying, whereas others have reported accelerated gastric emptying, particularly after consumption of a fatty meal. 42,43 In a previous study in Gunn rats, 30 we showed that the decrease in plasma UCB levels preceded the increase in fecal bilirubin excretion during Orl treatment. This observation does not support a significant role for an increased intestinal transit time to explain our present results.…”

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

“…Previous studies have only examined the effects of intragastric or intraduodenal administration of a lipase inhibitor (Orlistat), and have found that when administered with 30-55 g of stable triglyceride emulsions, CCK release is inhibited. [9][10][11][12] Hildebrand et al 9 demonstrated that intraduodenal perfusion of a 30 g olive oil solution resulted in a threefold increase in plasma CCK concentrations from basal levels during the first postprandial hour that remained elevated for the remaining 4 h. In contrast, plasma CCK concentrations did not increase significantly during the experiment when Orlistat was administered. 9 Thus adequate digestion of dietary triglycerides by pancreatic lipase to produce FFAs is necessary for the release of endogenous CCK in response to food intake, particularly in the immediate postprandial period.…”

“…Healthy nonobese subjects were included in the trial to allow for comparisons with studies that examined the effects of intragastric and intraduodenal, as opposed to oral, administration of Orlistat on physiological and behavioural satiety in healthy subjects. 7,[9][10][11][12] Obese subjects were also excluded from the trial to reduce any possible confounding effects of obesity on physiological and behavioural measures of appetite. 13,14 Experimental trial The subjects completed two randomised trials separated by 2 weeks, during which they ingested a test meal with Orlistat (120 mg) or placebo (2 g flour).…”

“…8 However, CCK is only released in response to adequate triglyceride hydrolysis by pancreatic lipase that increases intraduodenal long-chain FFA (4C10) concentrations. 7,[9][10][11][12] Both Borovicka et al 11 and Schwizer et al 12 demonstrated that intragastric administration of Orlistat with a stable emulsion of triglycerides (10% Intralipid), which reduced lipolysis by 75%, inhibited plasma CCK release. When administered intraduodenally, Orlistat also attenuated the CCK response to a triglyceride emulsion.…”

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

“…In conclusion, intraduodenal C12 dose-dependently modulated APD motility and gastrointestinal hormone release in healthy male subjects, whereas effects on energy intake were only apparent with the highest dose infused (0.4 kcal/min), possibly because only at this dose was modulation of APD motility and gastrointestinal hormone secretion sufficient for a suppressant effect on energy intake. 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.…”