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

Abstract

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.

Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal

“…Conversely, loxiglumide, a specific CCK-A receptor antagonist, stimulates calorie intake and feelings of hunger, and delays fullness. [4][5][6][7] These studies therefore provide evidence for a physiological role of CCK, acting via peripheral CCK-A receptors, in mediating satiation signals that reduce meal size and energy intake.…”

“…4 Conversely, loxiglumide, a specific CCK-A receptor antagonist, stimulates calorie intake and feelings of hunger, and delays fullness. [4][5][6][7] However, as already discussed, hydrolysis of dietary triglycerides by pancreatic lipase is necessary for the release and, presumably, the function of endogenous CCK. Indeed, Matzinger et al 7 demonstrated that intraduodenal administration of fat reduced the amount of food eaten at a subsequent meal (60 min after starting the perfusion) by 20%, corresponding to a 23% reduction in calorie intake.…”

Effect of the glycemic index of carbohydrates on day-long (10 h) profiles of plasma glucose, insulin, cholecystokinin and ghrelin

“…Dietary protein is the most satiating macronutrient in experimental meal settings (Poppitt et al, 1998), with high-protein meals increasing blood concentrations of CCK (Blom et al, 2006;Bowen et al, 2006). Fat (Matzinger et al, 1999) and to a lesser extent carbohydrate (Holt et al, 1992;Parker et al, 2005) also stimulate CCK production from I cells in the duodenum and jejunum (Buffa et al, 1978).…”

Voluntary consumption of ethyl oleate reduces food intake and body weight in rats

“…Numerous studies have demonstrated a role for CCK and other gut peptides in the reduction of food intake and the activation of satiety mechanisms following intraintetsinal infusions of fatty acids. These robust effects have been ameliorated by both vagotomy and CCK-A receptor antagonism (7,8,15,32). Taken together, these novel findings both demonstrate the potential clinical relevance of gut-initiated satiety mechanisms in the treatment of obesity, and suggest important information on the means to best initiate them.…”

“…Numerous studies have described a reduction in food intake following infusion of fatty acids directly into the small intestine: French et al demonstrated that upper intestinal infusions of 20% oil emulsions enriched with either stearic, oleic, or linoleic acid significantly reduced food intake compared controls infused with saline, and that this reduction in food intake was accompanied with increased plasma CCK concentrations (9); Meyer et al described reductions in food intake following intraintestinal infusions of either fatty or amino acids (16); Cox et al have reported that jejunal infusions of linoleic or oleic acid elicit increased satiety, decreased food intake and decreased body weight in rats (6). Matzinger et al demonstrated that this effect is mediated by cholecystokinin, abolishing the effects of intraduodenal fat infusions on food intake with a specific CCK-A receptor antagonist (15).…”