Cholecystokinin: Anorectic Peptide

Appetite regulation in humans is incredibly complex and involves complex feedback loops that pass from the gut to the central nervous system. These peptides interact with receptors in the hypothalamus, and this results in changes to subsequent food intake. The most well known afferent signal that affects the hypothalamus is perhaps insulin, but many others are known. A number of orectic peptides (appetite stimulating: here) and anorectic peptides (appetite suppressing: here) have been identified in humans and other mammals, but their interaction is complex and their full functions in many cases is not understood. Cholecystokinin is an intestinally secreted peptide that has been shown act as an afferent signal to the central nervous system in order to induce satiety. Insulin may sensitise the hypothalamus to the effects of cholecystokinin, demonstrating the interactive nature of these signal molecules. Cholecystokinin is secreted by the I cells of the mucosa of the small intestine.

Studies have investigated the appetite satiating effects of cholecystokinin in animals models and results from such studies confirm the role of cholecystokinin as an anorectic peptide. The role of cholecystokinin in humans has also been studied. For example, in ones study1, researchers infused a synthetic C-terminal octapeptide of cholecystokinin (cholecystokinin-8) into twelve healthy subjects and monitored their subsequent food intake at breakfast. The infusion of the synthetic version of cholecystokinin decreased food intake by mean value of 122 grams. In nine subjects food intake decreased by between 18 grams to 522 grams, and in three subjects food intake increase by between 73 and 94 grams. Cholecystokinin-8 also decrease the mean meal duration by 1.53 minutes, from 9.37 minutes to 7.84 minutes in the cholecystokinin and control groups, respectively. The authors reported that infusion of the synthetic cholecystokinin analogue did not produce any side effects in any of the subjects.

These results and others confirm that cholecystokinin is an effective anorectic agent and that likely acts as an afferent feedback signal to the hypothalamus to induce satiety. Other studies investigating the effects of cholecystokinin have shown that it is released from the I cells of the mucosa of the small intestine in response to undigested protein in the duodenum. Another role of cholecystokinin appear to be stimulation of the closure of the pyloric sphincter and in this way the emptying rate of the stomach is inhibited. Cholecystokinin may therefore function to ensure that protein digestion within the stomach is complete before the chyme within the antrum of the stomach is released to the rest of the gut. In this way the complete digestion of protein to shorter peptides within the stomach is ensured. The ability of high protein diets to cause satiety may therefore be explained by their role in determining stomach emptying rates, and it is likely that cholecystokinin plays an important role in this process.

Dr Robert Barrington’s Nutritional Recommendation: It is not necessary to infuse synthetic analogues of cholecystokinin to take advantage of its satiety inducing properties. High protein diets stimulate the release of cholecystokinin and induce satiety, and high protein diets have been shown to cause beneficial glycaemic and weight loss effects. Protein is the rate limiting factor in stomach emptying rates and eating enough protein to maintain a positive nitrogen balance is important to prevent unnecessary muscle loss, which can detrimentally affect resting metabolic rate. Around one gram per pound of lean body weight of high quality protein is recommended for most individuals wishing to improve their body composition.

RdB

1Kissileff, H. R., Pi-Sunyer, F. X., Thornton, J. and Smith, G. P. 1981. C-terminal octapeptide of cholecystokinin decreases food intake in man. American Journal of Clinical Nutrition. 34: 154-160

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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