Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.
OBJECTIVE
The hypothesis that cholecystokinin release requires adequate dietary fat digestion in the small intestine was investigated in 10 healthy volunteers, and the consequences of reduced fat hydrolysis on pancreaticobiliary secretions were assessed.


METHODS
Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses.


RESULTS
In the control without tetrahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fatty acid concentration averaged 60% of total fatty acids. Increasing doses of tetrahydrolipstatin induced a dose-dependent inhibition of duodenal lipase activity (P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreased to < 5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% (P < 0.01). Amylase and trypsin outputs were reduced by 77% and 59%, respectively, and bilirubin secretion was virtually abolished (P < 0.01).


CONCLUSIONS
These findings show that tetrahydrolipstatin prevents triglyceride hydrolysis and that plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion require adequate triglyceride digestion. These data also support the concept of negative feedback regulation of cholecystokinin secretion.
Hildebrand
P
P
Division of gastroenterology, University Hospital, Basel, Switzerland.
Petrig
C
C
Burckhardt
B
B
Ketterer
S
S
Lengsfeld
H
H
Fleury
A
A
Hadváry
P
P
Beglinger
C
C
D000328:Adult; D002766:Cholecystokinin / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology
D004041:Dietary Fats; D002766:Cholecystokinin; D008049:Lipase