Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects.
Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.
Enç
Feruze Yilmaz
FY
Department of Gastroenterology, Marmara University School of Medicine, Boğaziçi University, Istanbul, Turkey.
Ones
Tunç
T
Akin
H Levent
HL
Dede
Fuat
F
Turoğlu
H Turgut
HT
Ulfer
Gözde
G
Bekiroğlu
Nural
N
Haklar
Goncagül
G
Rehfeld
Jens F
JF
Holst
Jens J
JJ
Ulusoy
Nefise B
NB
Imeryüz
Neşe
N
D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating; D017615:Enteric Nervous System / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007783:Lactones / Q000008:administration & dosage*; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D000077403:Orlistat; D019894:Peptide YY / Q000378:metabolism; D011877:Radionuclide Imaging; D013270:Stomach / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007328:Insulin; D007783:Lactones; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D000077403:Orlistat