Academic literature on the topic 'Ileal brake activation'

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.

The site of intestinal fat delivery affects satiety and may affect food intake in humans. Animal data suggest that the length of the small intestine exposed to fat is also relevant. The aim of the present study was to investigate whether increasing the areas of intestinal fat exposure and the way it is exposed would affect satiety parameters and food intake. In the present single-blind, randomised, cross-over study, fifteen volunteers, each intubated with a naso-ileal tube, received four treatments on consecutive days. The oral control (control treatment) was a liquid meal (LM) containing 6 g fat ingested att = 0 min, with saline infusion att = 30–120 min. Experimental treatments were a fat-free LM att = 0 min, with either 6 g oil delivered sequentially (2 g duodenal,t = 30–60 min; 2 g jejunal,t = 60–90 min; 2 g ileal,t = 90–120 min), simultaneously (2 g each to all sites,t = 30–120 min) or ileal only (6 g ileal,t = 30–120 min). Satiety parameters (hunger and fullness) and cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured untilt = 180 min, whenad libitumfood intake was assessed. Only the ileum treatment reduced food intake significantly over the control treatment. The ileum and simultaneous treatments significantly reduced hunger compared with the control treatment. Compared with control, no differences were observed for PYY, CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had the most pronounced effect on food intake and satiety. Increasing the areas of intestinal fat exposure only affected hunger when fat was delivered simultaneously, not sequentially, to the exposed areas. These results demonstrate that ileal brake activation offers an interesting target for the regulation of ingestive behaviour.

The recently discovered SCFA-activated G-coupled protein receptors FFA receptor 2 and FFA receptor 3 are co-localised in l-cells with the anorexigenic ‘ileal brake’ gut hormone peptide YY, and also in adipocytes, with activation stimulating leptin release. Thus, SCFA such as acetate and propionate show promise as a candidate to increase satiety-enhancing properties of food. We therefore postulate SCFA may have a role in appetite regulation and energy homeostasis. SCFA can be delivered either directly within food, or indirectly via the colon by the provision of fermentable non-digestible carbohydrates. A review of studies investigating the effects of oral SCFA ingestion on appetite suggests that while oral SCFA ingestion is associated with enhanced satiety, this may be explained by product palatability rather than a physiological effect of SCFA. Colon-derived SCFA generated during microfloral fermentation have also been suggested to explain satiety-enhancing properties of non-digestible carbohydrates. However, findings are mixed from investigations into the effects of the prebiotic inulin-type fructans on appetite. Overall, data presented in this review do not support a role for SCFA in appetite regulation.

Abstract Background Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis and is highly expressed in enterocytes (EC). DGAT1 deficiency (DGAT1D) is a rare autosomal recessive protein losing enteropathy (PLE) classified as a congenital diarrheal disorder (CDD). Presumably, fat ingestion causes accumulation of DGAT1 substrates within the EC causing lipotoxicity-induced EC dysfunction and death. Aims Report a presentation of DGAT1D atypical for a CDD. Methods We present an infant with DGAT1D with protracted emesis and failure to thrive (FTT) in the absence of diarrhea despite enteral nutrition with varied fat containing formulas (FCF). Results A male infant presented with emesis and FTT requiring multiple admissions. He was initially diagnosed with cow’s milk protein allergy due to concurrent bloody stools, which resolved with hypoallergenic formula. Reportedly watery stools when exclusively breastfed became formed following switch to formula at 2 weeks of age. Interestingly, he subsequently required intermittent suppositories. However, emesis and malnutrition progressed, refractory to omeprazole, baclofen, and varied hypo- and non-allergenic FCF (all containing >0.02g/ml fat, mixtures of medium and long chain FA). He had persistently low serum albumin, ceruloplasmin, and IgG, but SA1AT was normal. TGs were normal, although not measured on FCF. Low fecal elastase (FE) normalized after nutritional support but sweat chloride was intermediate. CFTR sequencing revealed CFTR mutations S466X and R1070 in cis. TPN was started for severe malnutrition at 2 months. Emesis resolved while fasted or receiving enteral electrolyte solution. Endoscopic biopsies on FCF showed increased lamina propria cellularity, no villous abnormalities in the duodenum, chronic inflammation in the gastric body, and normal colonic mucosa. Whole exome sequencing at 2 months showed homozygous c.838C>T (p.Arg280Ter) mutations in DGAT1, explaining his clinical presentation and biochemical features of PLE. After diagnosis, he was started on Tolerex® formula (fat = 0.017g/ml), which was tolerated. Conclusions DGAT1D is classified as a CDD, with vomiting often reported. This case describes a unique presentation of this rare condition, with emesis the predominant symptom, and notable constipation, demonstrating the variable phenotype of this condition. Fat malabsorption may contribute to constipation by altering viscosity of luminal contents or activating the ileal brake. Thus, DGAT1D should be considered on the differential for congenital PLE, even without diarrhea. This case also demonstrates the limitations of stool testing in DGAT1D as random SA1AT concentrations may not reflect A1AT clearance in the diagnosis of PLE. Low FE has been detected in children with malnutrition or dietary restriction and has been reported in DGAT1D, where it likely represents a physiologic consequence of FTT. Funding Agencies None