Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women.
BACKGROUND
Reduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels.


METHODS
Forty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy.


RESULTS
Women treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. -0.1 ± 12.7 %, respectively). Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes.


CONCLUSIONS
The long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.
Department of Pathophysiology, Medical University of Silesia, Katowice, Poland. magols@esculap.pl
Magdalena
M
Olszanecka-Glinianowicz
Piotr
P
Dąbrowski
Piotr
P
Kocełak
Joanna
J
Janowska
Mike
M
Smertka
Krzysztof
K
Jonderko
Jerzy
J
Chudek
D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000077403:Orlistat; D019894:Peptide YY / Q000097:blood* / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D007328:Insulin; D007783:Lactones; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D000077403:Orlistat; D008049:Lipase