Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations

Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.

A glükagonszerű peptid-1 (GLP1) és a gyomor-bél rendszer. GLP1-receptor-agonisták – túlértékelt gyomor-, elfelejtődött bél- („ileal brake”) hatás?

Glucagon-like peptide-1 (GLP1) and their receptor agonists – beside their blood glucose lowering and central effects- affect also the gastrointestinal function in many respects. They slow down the stomach emptying, the motility of the small bowel and colon – this is the explanation for the “ileal brake” terminology –, stimulate the function of exocrine pancreatic acinar cells and increase amylase production. GLP1 receptor agonists belong to the defining tools of the blood glucose lowering therapy in type 2 diabetes. Their long- and short-acting derivatives have different influence on the fasting and the postprandial blood glucose, respectively. By introducing the term non-prandial and prandial type analogues – which seems to be forced in light of the newer data – the potential slowdown in gastric emptying is the center of interest, lately, however, especially in the case of long-acting GLP1 variants, at least such attention should be paid to controlling bowel function. The article reviews the physiological effects of GLP1 on the gastrointestinal tract and draws attention to the potential for the prevention of possible side effects through detailed patient information and dietary advises. Orv Hetil. 2019; 160(49): 1927–1934.