Ileal brake: A sensible food target for appetite control. A review

Abstract

With the rising prevalence of obesity and related health problems increases, there is increased interest in the gastrointestinal system as a possible target for pharmacological or food-based approaches to weight management. Recent studies have shown that under normal physiological situations undigested nutrients can reach the ileum, and induce activation of the so-called “ileal brake”, a combination of effects influencing digestive process and ingestive behaviour. The relevance of the ileal brake as a potential target for weight management is based on several findings: First, activation of the ileal brake has been shown to reduce food intake and increase satiety levels. Second, surgical procedures that increase exposure of the ileum to nutrients produce weight loss and improved glycaemic control. Third, the appetite-reducing effect of chronic ileal brake activation appears to be maintained over time. Together, this evidence suggests that activation of the ileal brake is an excellent long-term target to achieve sustainable reductions in food intake.

This review addresses the role of the ileal brake in gut function, and considers the possible involvement of several peptide hormone mediators. Attention is given to the ability of macronutrients to activate the ileal brake, and particularly variation attributable to the physicochemical properties of fats. The emphasis is on implications of ileal brake stimulation on food intake and satiety, accompanied by evidence of effects on glycaemic control and weight loss.

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.