ReviewIleal brake: A sensible food target for appetite control. A review
Introduction
Obesity is seen as a growing world-wide threat to health and prosperity. Reduced-energy diets are a widely-recommended, non-invasive primary treatment strategy for overweight and obesity. However, it is difficult for obese individuals to maintain the desired regime of dietary control in part because of the associated effects including feelings of hunger and food cravings. Compliance with weight control diet programmes could be improved, or at least less burdensome, if the associated hunger feelings were less pronounced. Because the gastrointestinal tract is host to various signals that regulate hunger, food intake and satiety [1], it is an obvious physiological target for developing food products and ingredients aimed at improving dietary compliance with a reduced energy intake. The relevant gastrointestinal signals are generated by various types of stimuli, such as distension of the luminal wall, presence of nutrients in the lumen or changes in pH, and lead to the activation of vagal afferents or release of gut peptides [2]. For example, entry of nutrients, especially fat and proteins, into the duodenum and jejunum results in release of cholecystokinin (CCK), a peptide that induces satiety and inhibits food intake [3], [4].
The entry of nutrients into the duodenum and jejunum activates the so-called duodenal and jejunal “brakes”: negative feedback mechanisms that influence the function of more proximal parts of the gastrointestinal tract. Activation of both of these feedback mechanisms results in reduction of food intake and inhibition of hunger, probably partly by inhibition of gastric emptying (thus contributing to enhanced and prolonged gastric distension) [5], [6], [7], [8], [9]. More distal in the GI tract, the ileal brake is a feedback mechanism that results in inhibition of proximal gastrointestinal motility and secretion. Animal and human studies show that activation of the ileal brake by local perfusion with nutrients increases feelings of satiety and reduces ad libitum food intake [10], [11], [12]. These results all point to a potential role of the ileal brake in the regulation of digestion, with direct or indirect impact upon eating behaviour and satiety.
This review considers 1) the role of the ileal brake in the regulation of gut function, including its physiological role and comparison to other intestinal braking mechanisms; 2) the mechanisms and mediators involved in activation of the ileal brake; 3) the effects of dietary components on ileal brake; and 4) the effects of ileal brake stimulation on eating behaviour. The paper focuses on data from research in humans, with data from animal models discussed where adequate human data are lacking.
Section snippets
Ileal brake and gut function
The ileal brake can be defined as a distal to proximal feedback mechanism to control transit of a meal through the gastrointestinal tract in order to optimise nutrient digestion and absorption [13]. While the original finding of ileal brake was confined to effects on jejunal motility and intestinal transit, since then the feedback concept was broadened to effects on gastric emptying, and pancreatic and biliary secretion. Spiller et al. [14] and Read et al. [15] were the first to describe such a
Mediators of the ileal brake
There is not yet a clear consensus on the physiological factors mediating the actions of the ileal brake. In general, nutrients in the small intestine influence gut function as well as satiety and food intake via activation of neural afferents or the release of gut peptides [3], [48], [49], [50], [51]. Of the gut peptides, Proglucagon-derived peptides (PGDP) and neurotensin have initially been proposed as hormonal mediators of the ileal brake [14], [15], [20]. Indeed, intravenous (iv)
Effect of dietary components on ileal brake
To date, studies in humans evaluating effects of ileal brake on food intake have employed only fat infusions. In order to asses the ability of different nutrient types to activate the ileal brake, it is necessary to refer to studies that used motility, transit and upper gut secretion as parameters.
Studies in animals indicate that all three macronutrients induce activation the ileal brake [94]. In humans, studies comparing the relative effects of macronutrients are limited in number and scope.
Satiety and food intake
Evidence from effects of ileal brake activation on satiety and food intake come from studies of ileal perfusion of fat and bariatric surgical procedures that result in increased exposure of the ileum to nutrients. While the nutrient perfusions studies mainly focus on acute, short-term stimulation of the ileal brake, the surgical model reflects a more chronic and sustained activation.
Conclusions
Apart from the role the ileal brake plays in the regulation of gastrointestinal motor and secretory function, activation of the ileal brake leads to a reduction in hunger and in food intake. Activation occurs after exposure of the ileum to fat, carbohydrates and protein. Suggested mediators include PYY, GLP-1 and vagal nerve stimulation. The inhibitory effect of ileal brake activation on satiety has been repeatedly demonstrated, but it is uncertain whether this effect results from direct
Acknowledgment
The authors would like to acknowledge the very significant contributions of an anonymous reviewer, who’s very comprehensive and thoughtful ideas greatly improved the quality and completeness of this review.
References (150)
- et al.
Satiety effects of the type A CCK receptor antagonist loxiglumide in lean and obese women
Biol Psychiatry
(1995) - et al.
Relation between postprandial satiation and antral area in normal subjects
Am J Clin Nutr
(1997) Gastric distension and gastric capacity in relation to food intake in humans
Physiol Behav
(1988)- et al.
Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers
Gastroenterology
(1985) - et al.
Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon
Gastroenterology
(1984) - et al.
Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY
Gastroenterology
(1993) - et al.
Effect of ileal infusion of intralipid on gastrointestinal transit, ileal flow rate, and carbohydrate absorption in humans after ingestion of a liquid meal
Gastroenterology
(1985) - et al.
The effect of terminal ileal triglyceride infusion on gastroduodenal motility and the intragastric distribution of a solid meal
Gastroenterology
(1990) - et al.
Intestinal control of human postprandial gastric function: the role of components of jejunoileal chyme in regulating gastric secretion and gastric emptying
Gastroenterology
(1981) - et al.
Intestinal transit and absorption of soy protein in dogs depend on load and degree of protein hydrolysis
J Nutr
(1997)
Protein absorption depends on load-dependent inhibition of intestinal transit in dogs
Am J Clin Nutr
Gastric emptying of solid food is most potently inhibited by carbohydrate in the canine distal ileum
Gastroenterology
Colonic inhibition of pancreatic and biliary secretion
Gastroenterology
Gastric satiation is volumetric, intestinal satiation is nutritive
Physiol Behav
A glucagon-like peptide-1 receptor agonist and an antagonist modify macronutrient selection by rats
J Nutr.
The physiological role of GLP-1 in human: incretin, ileal brake or more?
Regul Pept
Fat-induced ileal brake in the dog depends on peptide YY
Gastroenterology
The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway
Brain Res
Effect of peptide YY3–36 on food intake in humans
Gastroenterology
The effect of oxyntomodulin (glucagon-37) and glucagon on exocrine pancreatic secretion in the conscious rat
Peptides
Effect of naloxone on feedback regulation of small bowel transit by fat
Gastroenterology
Vagal efferent nerve-dependent inhibitory action of pancreatic polypeptide and peptide YY in conscious rats: comparison with somatostatin
J Auton Nerv Syst
Regulation of gastric emptying by ileal nutrients in humans
Gastroenterology
Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake
Am J Physiol Gastrointest Liver Physiol
The gut and energy balance: visceral allies in the obesity wars
Science
Effect of a low dose of intraduodenal fat on satiety in humans: studies using the type A cholecystokinin receptor antagonist loxiglumide
Gut
Evidence for the anorexia of aging: gastrointestinal transit and hunger in healthy elderly vs. young adults
Am J Physiol
Scintigraphic measurement of gastric emptying and ultrasonographic assessment of antral area: relation to appetite
Gut
The effect of macronutrients on gastric volume responses and gastric emptying in humans: a magnetic resonance imaging study
Am J Physiol Gastrointest Liver Physiol
Comparisons of the effects on satiety and eating behaviour of infusion of lipid into the different regions of the small intestine
Gut
Chemical specificities and intestinal distributions of nutrient-driven satiety
Am J Physiol
The ileal brake: a fifteen-year progress report
Curr Gastroenterol Rep
The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man
Gut
Effect of ileal infusion of lipid on jejunal motor patterns after a nutrient and nonnutrient meal
Am J Physiol
Further characterisation of the ‘ileal brake’ reflex in man—effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY
Gut
Intestinal transit is more potently inhibited by fat in the distal (ileal brake) than in the proximal (jejunal brake) gut
Dig Dis Sci
Comparison of ileal and duodenal brake mechanisms on satiety and gastrointestinal transport
Gastroenterology
The ileum and carbohydrate-mediated feedback regulation of postprandial pancreaticobiliary secretion in normal humans
Pancreas
Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion
Am J Physiol
Inhibition of human pancreatic and biliary output but not intestinal motility by physiological intraileal lipid loads
Am J Physiol Gastrointest Liver Physiol
Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans
Dig Dis Sci
Studies of intestinal digestion and absorption in the human
J. Clin. Invest
The intraluminal phase of fat digestion in man: the lipid content of the micellar and oil phases of intestinal content obtained during fat digestion and absorption
J Clin Invest
Effect of vagotomy on intraluminal digestion of fat in man
Gut
Fat absorption is not complete by midgut but is dependent on load of fat
Am. J. Physiol
Effects of lauric acid on upper gut motility, plasma cholecystokinin and peptide YY, and energy intake are load, but not concentration, dependent in humans
J Physiol
Role of small intestine in caloric compensations to oil premeals in rats
Am J Physiol
Duodenal and ileal nutrient deliveries regulate human intestinal motor and pancreatic responses to a meal
Am J Physiol
Modulation of human periodic interdigestive gastrointestinal motor and pancreatic function by the ileum
Pancreas
Glucagonlike peptide-1 (GLP-1) participation in ileal brake induced by intraluminal peptones in rat
Dig Dis Sci
Cited by (337)
Molecular cell types as functional units of the efferent vagus nerve
2024, Seminars in Cell and Developmental BiologyDietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions – a narrative review
2024, American Journal of Clinical Nutrition