The role of fat and cholecystokinin in functional dyspepsia

A subgroup of patients with functional dyspepsia arc characterised by heightened visceral sensitivity to mechanical distension of the stomach with a balloon. Small intestinal infusion of nutrients, particularly fat, exacerbates this hypersensitivity and also modulates sensations, such as hunger and fullness, in healthy subjects. Previous studies in healthy subjects suggest that cholecystokinin (CCK)-A and serotonergic (5-HT1) receptiors mediate, at least in part, the effects of lipid on gastrointestinal sensations. Recent studies have shown that duodenal fat infusion causes a dose dependent increase in the intensity of sensations and symptoms during gastric distension. However, fat digestion, achieved by using the specific lipase inhibitor tetrahydrolipstatin (THL) is necessary to promote the effects of fat on visceral sensation, gastric relaxation, and CCK release. The digestion products of fat interact with receptors in the small intestine. Long chain triglycerides (LCT) appear to be more potent than medium chain triglycerides (MCT) in inducing symptoms of fullness, nausea, and suppression of hunger. The effects of LCT are at least partially mediated by CCK as MCTs do not cause CCK release. In patients with functional dyspepsia, gastrointestinal symptoms induced by duodenal lipid infusion and gastric distension are alleviated by the CCK-A receptor antagonist dexloxiglumide. These studies provide important insights into the mechanisms underlying gastrointestinal perception in response to fat and the role of CCK in healthy subjects and patients with functional dyspepsia.