Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects.
The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 +/- 9.8 kg) or placebo (mean body weight 90.7 +/- 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecystokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 +/- 3.5 kg in the Orlistat group versus 3.0 +/- 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric emptying after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.
Drent
M L
ML
Department of Endocrinology, Free University Hospital, Amsterdam, Netherlands.
Popp-Snijders
C
C
Adèr
H J
HJ
Jansen
J B
JB
van der Veen
E A
EA
D001823:Body Composition / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage*; D004311:Double-Blind Method; D002149:Energy Intake; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors*; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000503:physiopathology*; D000077403:Orlistat; D010187:Pancreatic Hormones / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood; D016896:Treatment Outcome
D002395:Catecholamines; D004041:Dietary Fats; D006728:Hormones; D018972:Insulin-Like Growth Factor Binding Protein 3; D007783:Lactones; D010187:Pancreatic Hormones; D013963:Thyroid Hormones; D007334:Insulin-Like Growth Factor I; D000077403:Orlistat; D008049:Lipase