The food industry needs new, appropriate targets to aid development of functional foods for weight management in order to prevent obesity and to sustain a healthy body weight; this project aims to identify new targets. Primary focus is on the intestinal brake, the negative-feedback loop to more-proximal parts of the gastro-intestinal tract, with intestinal taste receptors as additional candidates.
The potency of various nutrients to induce an intestinal-brake mechanism was investigated. A first study showed that all macronutrients are equally able to reduce energy intake after ileal delivery. The second study investigated duodenal delivery of various tastants alone or in combination. Combining tastants reduced energy intake without stimulating satiety hormones. Two studies were performed. The first study focussed on the relevance of the nutrient delivery site for intestinal-brake activation and the second study evaluates the efficacy of repetitive ileal-brake activation. A proof-of-concept study, aiming at body-weight reduction by longer-term intestinal-brake activation in a real-life situation, has been developed.
Changes in molecular pathways, in the stomach and duodenum of obese patients subjected to a stomach-volume-reduction technique for body-weight reduction, were investigated. Transcriptome analysis revealed that expression of somatostatin was reduced in both the fundus and duodenum, suggesting reduced inhibition of satiety hormone secretion (ghrelin, GLP-1 and PYY). Gene sets related to inflammation were downregulated in the fundus; gene sets related to lipid metabolism were upregulated in the duodenum.
It was demonstrated, using tissue segments collected from various regions of the pig small intestine, that satiety hormones (GLP-1 and PYY) stimulate efficacy of the novel sweetener Rebaudioside A (Reb A). Research in cell lines and in ileal epithelial organoids (murine mini-guts) revealed that Reb A did not increase intracellular calcium levels. Furthermore, the sweet-taste receptor-specific g-protein was not expressed. This suggests that signalling pathways other than the classical sweet-taste receptor-signalling pathway could be involved in Reb A-induced GLP-1 release.
An artificial neural network was trained to predict feelings of hunger and satiety based on plasma profiles of the main satiety hormones CCK, GLP-1 and PYY. Predictions were quite accurate even when incomplete plasma profiles were available.
|Dissertations||2016 Intestinal Nutrient Sensing: a gut feeling for food||View summary|
|Dissertations||2016 Small intestinal targets involved in food intake regulation||View summary|
|Scientific papers in peer-reviewed journals||2015 Cholecystokinin regulates satiation independently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy||View summary|
|Scientific papers in peer-reviewed journals||2015 Capsaicin-induced satiety is associated with gastrointestinal distress but not with release of satiety hormones||View summary|