Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations. / Ellrichmann, Mark; Kapelle, Mario; Ritter, Peter R; Holst, Jens Juul; Herzig, Karl-Heinz; Schmidt, Wolfgang E; Schmitz, Frank; Meier, Juris J.
In: The Journal of clinical endocrinology and metabolism, Vol. 93, No. 10, 10.2008, p. 3995-8.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations
AU - Ellrichmann, Mark
AU - Kapelle, Mario
AU - Ritter, Peter R
AU - Holst, Jens Juul
AU - Herzig, Karl-Heinz
AU - Schmidt, Wolfgang E
AU - Schmitz, Frank
AU - Meier, Juris J
PY - 2008/10
Y1 - 2008/10
N2 - INTRODUCTION: 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.
AB - INTRODUCTION: 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.
KW - Administration, Oral
KW - Adult
KW - Animals
KW - Appetite
KW - Cholecystokinin
KW - Enzyme Inhibitors
KW - Gastric Emptying
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Intestines
KW - Lactones
KW - Lipase
KW - Peptide Fragments
KW - Peptide YY
KW - Placebos
KW - Postprandial Period
KW - Rats
KW - Satiety Response
KW - Time Factors
U2 - 10.1210/jc.2008-0924
DO - 10.1210/jc.2008-0924
M3 - Journal article
C2 - 18647814
VL - 93
SP - 3995
EP - 3998
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 10
ER -
ID: 132048491