Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations.
BACKGROUND
Intestinal lipase inhibition using tetrahydrolipstatin (Orlistat) has been widely used in the pharmacotherapy of morbid obesity. However, the effects of Orlistat on the secretion of appetite regulating gastrointestinal hormones and appetite sensations are still debated. We addressed whether Orlistat alters the secretion of glucagon-like peptide-1-(7-36)-amide (GLP-1), cholecystokinin (CCK), peptide YY (PYY), and ghrelin as well as postprandial appetite sensations.


METHODS
Twenty-five healthy human volunteers were examined with a solid-liquid test meal after the oral administration of Orlistat or placebo. Gastric emptying, gallbladder volume and the plasma levels of CCK, PYY, GLP-1, and ghrelin were determined and appetite sensations were measured using visual analogue scales.


RESULTS
Gastric emptying was accelerated by Orlistat administration (P < 0.0001), whereas gallbladder emptying was inhibited (P < 0.0001). Plasma levels of CCK (by approximately 53%), PYY (by approximately 40%), and GLP-1 (by approximately 20%) were significantly lowered by Orlistat (P < 0.001), whereas ghrelin levels were unaffected by Orlistat treatment (P = 0.18). Satiety and fullness were lowered by Orlistat (P < 0.0001), whereas appetite and prospective food consumption increased (P < 0.0001). The changes in CCK and PYY levels and the mean hunger ratings after Orlistat treatment were closely related to the inhibition of gallbladder motility.


CONCLUSIONS
Orlistat alters gastric and gallbladder emptying and reduces the postprandial secretion of GLP-1, PYY and CCK. These changes in gastrointestinal hormone concentrations may raise appetite sensations and increase food consumption and should therefore be considered as potential side effects when applying lipase inhibitors for the treatment of morbid obesity.
Ellrichmann
Mark
M
Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany. mark.ellrichmann@rub.de
Kapelle
Mario
M
Ritter
Peter R
PR
Holst
Jens J
JJ
Herzig
Karl-Heinz
KH
Schmidt
Wolfgang E
WE
Schmitz
Frank
F
Meier
Juris J
JJ
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D002766:Cholecystokinin / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors*; D000077403:Orlistat; D010446:Peptide Fragments / Q000097:blood*; D019894:Peptide YY / Q000097:blood*; D010919:Placebos; D019518:Postprandial Period / Q000187:drug effects*; D051381:Rats; D012528:Satiety Response / Q000187:drug effects; D013997:Time Factors
D004791:Enzyme Inhibitors; D007783:Lactones; D010446:Peptide Fragments; D010919:Placebos; D019894:Peptide YY; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D000077403:Orlistat; D008049:Lipase