Dose-dependent effects of cholecystokinin-8 (CCK-8) on pyloric motility, appetite and energy intake.

Abstract

CCK suppresses appetite and modulates gastrointestinal motility, however, the relationship between these parameters remains unclear. Furthermore, the effects of CCK on appetite may be due to nausea caused by supraphysiological CCK concentrations. We hypothesised that CCK would have dose-dependent effects on pyloric motility and appetite, in the absence of nausea. Healthy males (23±1 years; BMI 23±0.5 kg/m 2 ) were studied on 4 occasions in double-blind, randomised fashion. Appetite and pyloric pressures were measured during 120-min intravenous infusions of (i) saline (control), or CCK-8 at (ii) 0.33 (‘CCK0.33’), (iii) 0.66 (‘CCK0.66’) or (iv) 2 (‘CCK2’) ng/kg/min. At 90 min energy intake at a buffet meal was quantified. There was an effect of treatment on scores for desire-to-eat ( P <0.05). All CCK infusions decreased desire-to-eat when compared with control ( P <0.05), and their effects were dose-related ( R =0.7, P =0.05). No infusion-induced nausea. There was a treatment-by-time interaction for the number of isolated pyloric pressure waves (IPPWs) ( P =0.001). All CCK infusions increased IPPWs when compared with control; CCK0.66 and CCK2 between 0 and 90 min ( P <0.01), and CCK0.33 between 0 and 45 min ( P <0.05). Mean energy intake was less following both CCK0.66 (3630±550 kJ) and CCK2 (3319±359 kJ) when compared with control (3974±491 kJ). There was an inverse relationship between desire-to-eat and IPPWs ( R =−0.7, P <0.05), and a trend for a positive relationship between desire-to-eat and energy intake ( R =0.53, P =0.09). In conclusion (i) intravenous CCK has dose-related effects on pyloric motility and appetite, in the absence of nausea, and (ii) the stimulation of IPPWs may be a determinant of appetite suppression.