INHIBITION OF GASTRIC-EMPTYING IN RESPONSE TO INTESTINAL LIPID IS DEPENDENT ON CHYLOMICRON FORMATION

Lipid in the intestine initiates feedback inhibition of proximal gastr ointestinal function and food intake. In rats and humans, inhibition o f gastric emptying is mediated, at least in part, by cholecystokinin ( CCK)-A receptors, and in rats there is evidence for involvement of an intestinal vagal afferent pathway. The mechanism by which luminal lipi d acts to release CCK or activate vagal afferent nerve terminals is un clear. The role of chylomicron formation in this sensory transduction pathway has been investigated using the hydrophobic surfactant Pluroni c L-81 that inhibits chylomicron formation. Gastric emptying of liquid s was measured in awake rats fitted with a Thomas gastric fistula and a duodenal cannula. Intestinal perfusion of lipid induced a dose-depen dent inhibition of gastric emptying (6, 12, and 39% inhibition for 25, 50, and 100 mg lipid, respectively). Perfusion of lipid with Pluronic L-81 (2.8% wt/vol) reversed the lipid-induced inhibition of gastric e mptying. Pluronic L-63, a chemically similar surfactant that has no ef fect on chylomicron formation, had no effect on lipid-induced inhibiti on of gastric emptying. Per fusion of the intestine with lipid (100 mg ) increased plasma levels of CCK from 1.9 +/- 0.8 to 6.5 +/- 1 pM. Thi s increase was blocked by Pluronic L-81 but unaffected by L-63. These results provide evidence that chylomicron formation is important in th e signaling of lipid in the intestinal lumen to CCK endocrine cells an d to producing feedback inhibition of gastric emptying.