Daniel Matzinger

Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans

Intraduodenal fat inhibits gastric emptying and exerts early satiation in animals and humans, but it is not clear whether the effects are mediated by cholecystokinin (CCK) in humans. Here, we tested whether CCK-A receptors mediate the inhibition of fat on food intake. Two sequential, double-blind, crossover studies were performed in 24 male subjects. First, subjects received either intraduodenal fat or saline together with a preload of either water or banana shake. Second, 12 subjects received either intraduodenal fat or saline perfusion plus a concomitant infusion of saline or loxiglumide, a specific CCK-A receptor antagonist, together with a preload of banana shake. In both studies, subjects were free to eat and drink as much as they wished. Fat induced a reduction in calorie intake ( P < 0.05) compared with controls. Furthermore, a decrease in hunger feelings was observed. Infusion of loxiglumide abolished the effects of fat. Duodenal fat interacts with an appetizer to modulate energy intake in humans. This effect is mediated by CCK-A receptors.

The effect of cholecystokinin in controlling appetite and food intake in humans

The present review of the satiating effect of cholecystokinin in humans has revealed that cholecystokinin is a physiological satiety factor in humans. The results demonstrate the efficacy of the satiating actions of exogenous and endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be estimated until further studies are performed that demonstrate the efficacy of CCK analogues for decreasing body weight, and the safety of CCK when administered repetitively for prolonged periods.

Role of Free Fatty Acids in Regulating Gastric Emptying and Gallbladder Contraction

The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases, in inhibiting fat digestion is not completely understood. Therefore we studied the effect of orally and duodenally administered orlistat on gastric emptying, cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males, gastric emptying of solids and fat were quantified scintigraphically, gallbladder contraction by ultrasound and CCK release by radioimmunoassay. Three studies were performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3) duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat (T50% accelerated by 16 and by 22%, p< 0.05, respectively) were significantly faster after duodenal perfusion of orlistat; gallbladder contraction and CCK release were reduced under these conditions (p < 0.005, respectively). With oral orlistat no significant effect was documented on these parameters. We conclude that fat hydrolysis is essential in the regulation of fat-induced gastric emptying and gallbladder contraction.

Effects of a Preload on Reduction of Food Intake by GLP-1 in Healthy Subjects

Background/Aims: Glucagon-like peptide-1 (GLP-1) inhibits food intake in animals and humans. Whether GLP-1 interacts with other satiety signals to modulate food intake is unknown. We investigated therefore in healthy volunteers the potential interactions of GLP-1 with signals from the stomach in regulating food intake. Methods: Three sequential, double-blind, crossover studies were performed in male subjects: (1) 12 subjects underwent four experiments (preloads) 20 min before meal intake; (2) 12 volunteers received intravenous (i.v.) GLP-1 (0.9 pmol/kg/min) or saline; (3) subjects received i.v. GLP-1 or saline (control) together with a preload of either 400 ml water or 400 ml protein shake. The effect of these treatments on food intake and feelings of hunger was quantified. Subjects were free to eat and drink as much as they wished. Results: GLP-1 induced a reduction in food and calorie intake (p < 0.005) compared to controls. If combined with a protein preload, the inhibitory effect of GLP-1 on food intake was markedly increased (p < 0.001). Furthermore, a decrease in hunger feelings and an increase in satiety feelings was documented. Conclusion: GLP-1 interacts with signals from the stomach to modulate energy intake in humans. The signal is only initiated by nutrient-based distension, but not with gastric distension of the fundus alone.