Regulation of fat-stimulated neurotensin secretion in healthy subjects.
BACKGROUND
Cholecystokinin (CCK) and neurotensin are stimulated during meal intake by the presence of fat in the small intestine. The sequence of events suggests that fat hydrolysis is crucial for triggering the release.


OBJECTIVE
The aim of this study was to investigate whether CCK mediated the effect of intraduodenal (ID) fat on neurotensin secretion via CCK-1 receptors.


METHODS
This was a single center study; 34 male volunteers were studied in consecutive, randomized, double-blind, cross-over studies.


METHODS
CCK and neurotensin release were quantified in: 1) 12 subjects receiving an ID fat infusion with or without 60 mg orlistat, an irreversible inhibitor of gastrointestinal lipases, in comparison to vehicle; 2) 12 subjects receiving ID long chain fatty acids (C18s), ID medium chain fatty acids, or ID vehicle; and 3) 10 subjects receiving ID C18 with and without the CCK-1 receptor antagonist dexloxiglumide or ID vehicle plus iv saline (placebo). Hormone concentrations were measured by specific RIA systems.


RESULTS
ID fat induced a significant increase in CCK and neurotensin concentrations (P < 0.001-0.002). Inhibition of fat hydrolysis by orlistat abolished both effects. C18 stimulated CCK and neurotensin release (P < 0.001, respectively), whereas medium chain fatty acid was ineffective. Dexloxiglumide administration partially blocked the effect of C18 on neurotensin; the effect was only present in the first phase of neurotensin secretion.


CONCLUSIONS
Generation of C18 through hydrolysis of fat is a critical step for fat-induced stimulation of neurotensin in humans; the signal is in part mediated via CCK release and CCK-1 receptors.
Drewe
Juergen
J
Clinical Research Centre, Department of Research, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
Mihailovic
Svetlana
S
D'Amato
Massimo
M
Beglinger
Christoph
C
D000328:Adult; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D005223:Fats / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009496:Neurotensin / Q000097:blood / Q000378:metabolism*; D010421:Pentanoic Acids / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology
D005223:Fats; D010421:Pentanoic Acids; D011949:Receptors, Cholecystokinin; D009496:Neurotensin; C103490:dexloxiglumide; D002766:Cholecystokinin