Role of lipase in the regulation of postprandial gastric acid secretion and emptying of fat in humans: a study with orlistat, a highly specific lipase inhibitor

Abstract

Background and aims: To investigate the importance of lipase on gastric functions, we studied the effects of orlistat, a potent and specific inhibitor of lipase, on postprandial gastric acidity and gastric emptying of fat.

Methods: Fourteen healthy volunteers participated in a double blind, placebo controlled, randomised study. In a two way cross over study with two test periods of five days, separated by at least 14 days, orlistat 120 mg three times daily or placebo was given with standardised daily meals. In previous experiments we found that this dose almost completely inhibited postprandial duodenal lipase activity. Subjects underwent 28 hour intragastric pH-metry on day 4, and a gastric emptying study with a mixed meal (800 kcal) labelled with (999m)Tc sulphur colloid (solids) and (111In)thiocyanate (fat) on day 5. Gastric pH data were analysed for three postprandial hours and the interdigestive periods.

Results: Orlistat inhibited almost completely (by 75%) lipase activity and accelerated gastric emptying of both the solid (by 52%) and fat (by 44%) phases of the mixed meal (p<0.03). Orlistat increased postprandial gastric acidity (from a median pH of 3.3 to 2.7; p<0.01). Postprandial cholecystokinin release was lower with orlistat (p<0.03).

Conclusion: Lipase has an important role in the regulation of postprandial gastric acid secretion and fat emptying in humans. These effects might be explained by lipolysis induced release of cholecystokinin.

Figure 1

Duodenal outputs of pancreatic lipase (HPL) after intragastric instillation of triglycerides (Intralipid) with placebo or orlistat. Values are mean (SEM) of six subjects.

Figure 2

Median intragastric pH during the 28 hour measurements in eight subjects who received placebo or orlistat. B, breakfast; L, lunch; D, dinner.

Figure 3

Box-whisker plots of postprandial gastric pH (three hour periods) in subjects who received placebo or orlistat. Boxes represent the medians and interquartile ranges, the error bars the 90% and the dots the 95% confidence intervals. p<0.01.

Figure 4

Gastric emptying of the proximal (left) and distal (right) stomach regions of the ¹¹¹In-labelled fat phase and ^99mTc-labelled solid phase with placebo. Values are mean (SEM) of eight subjects.

Figure 5

Gastric emptying of the ^99mTc-labelled solid phase (left) and ¹¹¹In-labelled fat phase (right) with placebo and orlistat. Values are mean (SEM) of eight subjects.