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.
OBJECTIVE
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).


CONCLUSIONS
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.
Borovicka
J
J
Gastroenterology and Nuclear Medicine Departments, University Hospitals, Lausanne and Zurich, Switzerland.
Schwizer
W
W
Guttmann
G
G
Hartmann
D
D
Kosinski
M
M
Wastiel
C
C
Bischof-Delaloye
A
A
Fried
M
M
D000328:Adult; D002766:Cholecystokinin / Q000097:blood; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000502:physiology; D005755:Gastrins / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D000077403:Orlistat; D019518:Postprandial Period
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005755:Gastrins; D007783:Lactones; D002766:Cholecystokinin; D000077403:Orlistat; D008049:Lipase