Antropyloroduodenal, cholecystokinin and feeding responses to pulsatile and non-pulsatile intraduodenal lipid infusion R. VOZZO, Y- C. SU, R. J . FRASER, G. A. WITTERT, M. HOROWITZ, C. H. MALBERT,  A. SHULKES, à T. VOLOMBELLOà &I . M. CHAPMAN University of Adelaide, Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia  Unite de Flux Digestifs, Institut National de la Recherche Agronomique, St Gilles, France àUniversity of Melbourne, Department of Surgery, Austin Campus, Melbourne, Australia Abstract The contribution of the pulsatile nature of gastric emptying to small intestinal feedback mecha- nisms modulating antropyloroduodenal motility and appetite is unknown. On separate days, eight healthy male volunteers (18±34 years) received randomized, single-blind, intraduodenal (ID) infusions of 10% Intralipid (2 kcal min )1 ), either continuously [CID], or in a pulsatile manner [PID] (5 s on/15 s off) and 0.9% saline (control) administered continuously, each at a rate of 1.8 mL min )1 for 3 h. During each infusion, subjective ratings of appetite were assessed and antropyloroduodenal pressures recorded with a 16- lumen manometric assembly incorporating a pyloric sleeve sensor. Plasma cholecystokinin was measured from blood collected at regular intervals throughout the infusion. At the end of each infusion the mano- metric assembly was removed, subjects were offered a buffet meal and the energy and macronutrient content of the meal was measured. Both ID lipid infusions stimulated isolated pyloric pressure waves (IPPWs) (P < 0.001) and basal pyloric pressure (P < 0.01) and suppressed antral (P < 0.05) and duodenal (P < 0.05) pressure waves when compared to controls; there was no difference in the effects of CID and PID lipid on antropyloroduodenal pressures. Infusions of lipid signi®cantly increased plasma CCK concentrations (P < 0.05) compared with saline, but concentrations were not different between the two modes of lipid delivery (P > 0.05, CID vs. PID). Both intraduodenal lipid infusions decreased hunger (P < 0.05), increased fullness (P < 0.05) and reduced energy intake (P < 0.05) when compared with controls; again there was no difference between CID and PID lipid. We conclude that at the infusion rate of  2 kcal min )1 , the acute effects of intraduodenal lipid on antropylo- roduodenal pressures, plasma CCK concentration and appetite are not modi®ed by a pulsatile mode of lipid delivery into the duodenum. Keywords motility, pylorus, sensation. INTRODUCTION The interaction between nutrients and mucosal chemoreceptors in the small intestine plays a major role in the regulation of both gastric emptying 1±4 and appetite. 5±7 Exposure of the small intestine to nutrients slows gastric emptying via a decrease in propulsive forces, 2,8 together with an increased resistance to transpyloric ¯ow. 2,9,10 Stimulation of pyloric motility may be the most important of these mechanisms; increases in basal pyloric pressure and isolated pyloric pressure waves are associated with cessation of trans- pyloric ¯ow. 4 Intraduodenal infusions of triglyceride also reduce appetite and subsequent food intake 5,6,11,12 and stimulate cholecystokinin (CCK) secretion. 13 The latter is believed to play a major role in the regulation of gastroduodenal motor activity, because intravenous CCK administration stimulates pyloric motility in humans 14 and the CCK-A receptor antagonist, loxi- glumide, restores tonic and phasic gastric activity during lipid infusions, 15 thus directly implicating CCK as a mediator of lipid-induced gastric contractile Ó 2002 Blackwell Science Ltd 25 Address for correspondence Dr R Fraser, University of Adelaide, Department of Medicine, Royal Adelaide Hospital, Adelaide SA 5000, Australia. Tel.: + 61 8 8222 5502; fax: + 61 8 8223 3870; e-mail: robert.fraser@adelaide.edu.au Received: 1 March 2001 Accepted for publication: 20 August 2001 Neurogastroenterol. Mot. (2002) 14, 25±33