Intestinal nutrient sensing : a gut feeling for food
Wielen, N. van der - \ 2016
Wageningen University. Promotor(en): Renger Witkamp, co-promotor(en): Jocelijn Meijerink; Henk F.J. Hendriks. - Wageningen : Wageningen University - ISBN 9789462576995 - 200
obesity - hormones - intestines - gastrointestinal hormones - pancreozymin - vasoactive intestinal peptide - sensing - in vivo experimentation - animal models - in vitro - gastric bypass - food - weight reduction - stevia rebaudiana - release - obesitas - hormonen - darmen - maagdarmhormonen - pancreozymine - vasoactief intestinaal peptide - aftasten - in vivo experimenten - diermodellen - in vitro - buik bypass - voedsel - gewichtsvermindering - stevia rebaudiana - vrijgeven
The alarming increase in obesity rates creates an urgent need for effective prevention and treatment strategies. The most effective treatment for obesity today is bariatric surgery. Bariatric surgery comprises a number of different procedures having in common that they induce weight loss and alter gut hormone release. Gut hormones are well known for their effects on food intake behavior and their role in weight loss after bariatric surgery is undeniable. In addition, the therapeutic use of GLP-1 (Glucagon-Like Peptide-1) analogues including liraglutide in type II diabetes and obesity is on the rise. This underlines why gut hormones are considered promising targets for the development of new treatment strategies against obesity and its comorbidities.
The secretion of gut hormones, among which GLP-1, is influenced by nutrient ingestion. The interactions of dietary components or their breakdown products with receptors and transporters located on the enteroendocrine cells of the intestinal tract can induce their release, a process called intestinal nutrient sensing. In this thesis, we aimed to further elucidate intestinal nutrient sensing mechanisms on a cellular level. First, the regional expression of several gut nutrient sensing related genes along the intestinal tract was assessed in three commonly studied species, namely mouse, pig and man. Gene expression of receptors, transporters and peptides involved in nutrient sensing shows a distinctive distribution pattern along the small intestine, which is in the distal small intestine highly similar between the species. Subsequently, we sought to investigate if this expression was changed after a weight loss inducing bariatric procedure. By whole transcriptome analysis, we showed that upper gastrointestinal tissue expression of genes associated with nutrient sensing was hardly changed. In contrast, a considerable reduction in inflammatory pathways was observed.
Next, we sought to investigate the effects of the non-caloric sweetener rebaudioside A. This Stevia rebaudiana-derived compound was approved on the European market in 2011. As there is still some controversy about the effects of sweeteners in general on GLP-1 release, we investigated the effects of this specific sweetener. Because of the short half-life of GLP-1, the effect of nutrient stimulation was mainly studied in ex vivo and in vitro models in which local intestinal hormone release could be determined. A two dimensional gut model using intestinal organoids derived from murine intestinal crypts was developed to study location-specific hormone secretion. Rebaudioside A was found to induce GLP-1 and PYY release ex vivo from porcine intestinal tissue and in two dimensional organoids. This induction of the release was specific for the intestinal location, with the ileum being most potently stimulated by rebaudioside A. Moreover, prolonged exposure to rebaudioside A increased enteroendocrine cell numbers in two dimensional organoids. When studying the underlying mechanism in enteroendocrine STC-1 cells, we concluded that rebaudioside A-induced GLP-1 release was independent of the sweet taste receptor.
The studies presented in this thesis add to our understanding the role of receptors and other molecular structures that are likely to be involved in nutrient sensing and the modulation of gut hormone release. What we know now is that several factors play a role in gut hormone release. This includes not only the nature and dose of the active compound(s), but also the location and timing of its (their) interactions with receptors and other targets along the gastrointestinal tract. We have shown that rebaudioside A may be a potential compound to induce gut hormone release in vivo, especially when applied to the distal small intestine. Therefore, rebaudioside A may be a promising compound to influence food intake, possibly most potent when delivered in the ileum.
Ileal brake activation: macronutrient-specific effects on eating behavior?
Avesaat, M. van; Troost, F.J. ; Ripken, D. ; Hendriks, H.F. ; Masclee, A.A.M. - \ 2015
International Journal of Obesity 39 (2015). - ISSN 0307-0565 - p. 235 - 243.
glucagon-like peptide-1 - food-intake - hormone-release - energy-intake - antropyloroduodenal motility - gastrointestinal hormones - intestinal motility - duodenal glucose - plasma-levels - healthy-men
Background:Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown.Objective:The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control.Design:This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4¿kg¿m-2) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7¿kcal), low-dose casein ((LP) 17.2¿kcal) or high-dose casein ((HP) 51.7¿kcal), low-dose sucrose ((LC) 17.2¿kcal) and high-dose sucrose ((HC) 51.7¿kcal), over a period of 90¿min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals.Results:Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7¿kcal, P
Regulation of food intake : a focus on ghrelin
Blom, W.A.M. - \ 2005
Wageningen University. Promotor(en): Frans Kok; G. Schaafsma, co-promotor(en): H.F.J. Hendriks. - - 216
voedselopname - eetlustcontrole - verzadigdheid - honger - maagdarmhormonen - food intake - appetite control - satiety - hunger - gastrointestinal hormones
The number of people with (severe) overweight is increasing. More insight into the mechanism of food intake may help to develop foods for weight maintenance. There are indications that ghrelin is an important hunger signal. The role of ghrelin in the regulation of food intake was investigated in human volunteers at TNO Quality of Life in Zeist, in collaboration with the department of Human Nutrition of Wageningen University. Our studies showed that changes in ghrelin concentrations were related to changes in appetite, but these changes did not predict food intake. Suppression of ghrelin concentrations, however, did predict initiation of the next meal. Such suppression of ghrelin appears to depend on type of macronutrient and energy content of a meal. We conclude that ghrelin is a hunger signal that does not determine meal size (satiation), but that regulates next meal initiation (satiety). Foods that contain nutrients (for example dairy protein) that effectively suppress ghrelin concentrations, may help prevent overweight and obesity.