HYDROLYSIS OF DIETARY-FAT BY PANCREATIC LIPASE STIMULATES CHOLECYSTOKININ RELEASE

Background & Aims: The hypothesis that cholecystokinin release require s adequate dietary fat digestion in the small intestine was investigat ed in 10 healthy volunteers, and the consequences of reduced fat hydro lysis on pancreaticobiliary secretions were assessed. Methods: Fat hyd rolysis was inhibited by intraduodenal perfusion of tetrahydrolipstati n, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute bas al period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses. Results: In the control without tetr ahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fat ty acid concentration averaged 60% of total fatty acids. increasing do ses of tetrahydrolipstatin induced a dose-dependent inhibition of duod enal lipase activity (P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreas ed to <5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% (P < 0.01). Amylase and trypsin outputs were reduce d by 77% and 59%, respectively, and bilirubin secretion was virtually abolished (P < 0.01). Conclusions: These findings show that tetrahydro lipstatin prevents triglyceride hydrolysis and that plasma cholecystok inin release, gall-bladder emptying, and pancreatic enzyme secretion r equire adequate triglyceride digestion. These data also support the co ncept of negative feedback regulation of cholecystokinin secretion.