Activation of gastrointestinal bitter taste receptors suppresses food intake and stimulates secretion of gastrointestinal peptide hormones in healthy men

Abstract

Introduction: Gut chemosensory mechanisms, particularly those involved in detecting and relaying to the brain the chemical composition of food during digestion, play important roles in controlling gut function and appetite regulation. Activation of bitter taste receptors, expressed throughout the gastrointestinal tract by enteroendocrine cells, may modulate feeding behaviour via the release of gut peptide hormones, a mechanism we have termed the “bitter brake”. Our aim was to establish the efficacy and site of action of a bitter, plant-based, non-nutritive ingredient (Amarasate™ extract) to modify acute energy intake, subjective ratings of appetite and gut peptide hormone concentrations. Methods: Twenty healthy lean (BMI = 23.5 ± 0.3 kg/m2) male volunteers participated in a randomised three treatment, double blind, cross-over study with a 1 week washout between treatments. Overnight fasted participants were cannulated and provided with a standardised 2MJ Breakfast (0900h). Treatments (500 mg Amarasate extract or Placebo) were administered in low pH resistant (1100h) or standard (1130h) hypromellose capsules for targeted duodenal or gastric release, respectively. To maintain treatment blinding, placebo capsules were also administered as part of each treatment. Energy intake was recorded at an ad lib lunch (1200h) and snack (1400h). Blood samples and visual analogue scale subjective ratings of appetite were taken throughout the day. Results: Compared with placebo, both gastric and duodenal delivery of the Amarasate extract stimulated significant increases (p < 0.05) in the gut peptide hormones CCK, GLP-1 and PYY while significantly reducing (p < 0.05) total (lunch plus snack) ad lib meal energy intake by 911 (± 308) kJ and 944 (± 309) kJ, respectively. However, no significant treatment effects were observed for any subjective ratings of appetite or nausea. Conclusion: We have demonstrated that activation of the “bitter brake” mechanism by a bitter plant extract can stimulate the release of gut peptide hormones involved in appetite regulation and suppress subsequent feeding behaviour in healthy men. Acknowledgement: This study was funded by the NZ Ministry of Business, Innovation & Employment (C11X1004).