Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

OBJECTIVE: To examine the short-term effects of a lipase inhibitor (Orlistat) on physiological and behavioural measures of appetite in response to a high-fat meal. DESIGN: Randomised, single blind, placebo-controlled, crossover trial. SUBJECTS: A total of 19 healthy nonobese male subjects. PROCEDURES: After an overnight fast, subjects ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10% protein) with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite, as assessed by a standard line scale, and plasma cholecystokinin (CCK) concentrations were measured prior to and every hour after the test meal for 4 h. Thereafter, subjects ingested a quantified, but self-selected portion of a standardised lunch (15% protein, 37% fat and 45% CHO), before completing a final line scale questionnaire. RESULTS: The CCK response to the test meal was negatively correlated with BMI in both the Orlistat and placebo trials (R = -0.69 and -0.65, P < 0.01). Orlistat administration did not significantly alter the CCK response to the test meal (6.30 ± 3.27 vs 7.36 ± 3.94 pM min, for Orlistat and placebo, P = 0.193). Similarly, the line scale measures of appetite and subsequent intake (520 ± 205 vs 554 ± 197 g, P = 0.48) were not different between the trials. CONCLUSION: Orlistat administration did not alter short-term physiological or behavioural measures of satiety in response to a high-fat meal in healthy, nonobese subjects. The CCK response to a test meal may be partly determined by BMI.