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Su2071 The Effect of the Bitter Taste Receptor Agonist Denatonium Benzoate on Gastric Emptying, Satiety and Return of Hunger After a Meal in Healthy Volunteers
AGA Abstracts
Figure 1. Delta hunger ratings 60 minutes after compound administration. Data are represented as mean±SEM. Su2071 The Effect of the Bitter Taste Receptor Agonist Denatonium Benzoate on Gastric Emptying, Satiety and Return of Hunger After a Meal in Healthy Volunteers Sofie Verschueren, Pieter Janssen, Christopher N. Andrews, Kristin Verbeke, Inge Depoortere, Jan F. Tack
SCBM, spontaneous complete bowel movement; SBM, spontaneous bowel movement; PAQSYM, patient assessment of constipation - symptoms; RR, relative risk. Su2070
Introduction: Intragastric administration of a mixture of bitter receptor agonists decreased food intake in mice (PNAS 108(5): p2094). We set out to investigate the effect of the bitter receptor agonist denatonium benzoate (DB) on gastric emptying, satiety and return of hunger after a meal in healthy volunteers. Methodology: After an overnight fast, 19 healthy volunteers received an intragastric administration of DB (1 μmol/kg) or placebo. 30 minutes hereafter, a meal consisting of two pancakes (500 kcal) was consumed by the volunteers within 15 minutes. Every 15 minutes, starting from just before the treatment until 4 hours after the meal, volunteers scored their feeling of hunger, satiety and expected amount to eat on a 100 mm visual analogue scale. Data was compared as areas under the curve (AUC) from the start of the treatment until 4 hours after the meal (mean ± sem) and compared using a paired t-test. In 9 subjects, pancakes ingested on both occasions were labeled with sodium 13C-octanoate. Every 15 minutes, starting from just before the treatment until 4 hours after the meal, volunteers exhaled in an exetainer that was stored in the fridge for later analysis. In addition they scored their feeling of hunger, satiety and expected amount to eat on a 100 mm visual analogue scale.The 13CO2-content of the breath samples was analysed using isotope-ratio mass spectrometry. The 13CO2 excretion data were analysed by non-linear regression to allow curve fitting and calculation of the gastric half-emptying time (t½). Results: DB treatment did not alter feelings of hunger, satiation and expected amount to eat in the time frame before the meal (for all scores p .0.5). Consumption of the meal was accompanied by a rise of satiety and a decrease of hunger and expected amount to eat. Thereafter, satiety gradually decreased, while hunger and expected amount to eat increased. During the measuring period, scores for satiety were significantly higher after DB treatment as compared to placebo (AUC: 9596 ± 1293 mm*min vs. 6276 ± 1022 mm*min respectively; p,0.001). During the entire study period, volunteers felt less hungry and also the expected amount to eat was lower after DB treatment as compared to placebo [AUC hunger: 8513 ± 1186 mm*min vs. 11461 ± 1124 mm*min respectively (p ,0.01), AUC expected amount to eat: 9431 ± 950 mm*min vs. 12339 ± 969 mm*min respectively (p ,0.05)]. T1/2 between treatments was not different (103 ± 7 min for placebo vs. 100 ± 9 min for DB; p=0.7). Conclusion: Intragastric administration of the bitter receptor agonist denatonium benzoate before a meal increases satiety and delays the return of hunger up to 4 hours after the meal, although gastric emptying rate is not affected.
In Man Intragastric Administration of the Bitter Compound Denatonium Benzoate Decreases Hunger and the Occurrence of Gastric Phase III in the Fasting State Eveline Deloose, Maura Corsetti, Lukas Van Oudenhove, Inge Depoortere, Jan F. Tack Background: In mice, intragastric administration of a mixture of bitter agonists, including denatonium benzoate (DB), induced a prolonged suppression of food intake (Janssen, PNAS 2011). We recently reported a close correlation between gastric phase 3 (ph3) of the migrating motor complex (MMC) and hunger peaks (Deloose, DDW 2012).The aim of this study was to investigate the effect of DB on the occurrence of ph3 and hunger ratings in man. Methods: After an overnight fast, 11 healthy volunteers (6 men; 26±8 years; 24±2kg/m2) underwent a 36-channel antroduodenal high resolution manometry twice, with at least one week interval. Fasting motility was recorded for a full MMC cycle (2 ph3). 20 min after the occurrence of the 2nd ph3, DB (1μmol/kg) or placebo was administered intragastrically in a doubleblind randomized fashion through a nasogastric tube, to bypass the tongue. Motility recording continued until the next ph3 or 3 hrs. Subjects scored hunger every 5 min on a 10 cm visual analogue scale (VAS). Statistical analysis: A baseline hunger score was calculated by averaging VAS ratings during 10 min before administration of DB or placebo. This baseline score was subtracted from the hunger rating at each time point until 60 min after administration.The resulting delta hunger VAS scores were entered as the dependent variable in a linear mixed model analysis with time and administered agent (DB vs placebo) as continuous and categorical independent variables, respectively. The effect of interest is the interaction between time and agent, representing the difference in linear slope of the delta hunger scores between DB and placebo. Proportions were analyzed using Chi-square. Data are mean±SEM. Results: Baseline hunger scores did not differ between placebo and DB (58±9 vs 47±8 mm VAS; p=0.7). The slopes of delta hunger differed significantly between placebo and DB (time-by-agent interaction effect p=.0003, fig 1). While mean hunger ratings remained stable after administration of placebo (slope of delta hunger 0.03±0.03; p=.2), a progressive significant decrease in hunger occurred after DB (slope of delta hunger -0.11±0.03; p= .0012).The interval between baseline ph3 (98±19 vs 85±14 min; p=.8) as well as their origin (58% vs 57% gastric; p=.9) did not differ significantly between the two treatment days. During the 60 min interval after placebo, a ph3 occurred in 36% of the volunteers compared to only 11% after DB (p ,.0001). 75% of the ph3 were gastric after placebo compared to 0% after DB (p,.0001). DB was generally well tolerated, with only 1 subject reporting abdominal cramps on the night after the experiment. Conclusions: Administration of DB decreases hunger ratings and inhibits the occurrence of ph3 with a gastric origin. These data suggest potential involvement of GI bitter taste receptors in the control of hunger and interdigestive motility in man.
AGA Abstracts
S-548
Figure 1. Delta hunger ratings 60 minutes after compound administration. Data are represented as mean±SEM. Su2071 The Effect of the Bitter Taste Receptor Agonist Denatonium Benzoate on Gastric Emptying, Satiety and Return of Hunger After a Meal in Healthy Volunteers Sofie Verschueren, Pieter Janssen, Christopher N. Andrews, Kristin Verbeke, Inge Depoortere, Jan F. Tack
SCBM, spontaneous complete bowel movement; SBM, spontaneous bowel movement; PAQSYM, patient assessment of constipation - symptoms; RR, relative risk. Su2070
Introduction: Intragastric administration of a mixture of bitter receptor agonists decreased food intake in mice (PNAS 108(5): p2094). We set out to investigate the effect of the bitter receptor agonist denatonium benzoate (DB) on gastric emptying, satiety and return of hunger after a meal in healthy volunteers. Methodology: After an overnight fast, 19 healthy volunteers received an intragastric administration of DB (1 μmol/kg) or placebo. 30 minutes hereafter, a meal consisting of two pancakes (500 kcal) was consumed by the volunteers within 15 minutes. Every 15 minutes, starting from just before the treatment until 4 hours after the meal, volunteers scored their feeling of hunger, satiety and expected amount to eat on a 100 mm visual analogue scale. Data was compared as areas under the curve (AUC) from the start of the treatment until 4 hours after the meal (mean ± sem) and compared using a paired t-test. In 9 subjects, pancakes ingested on both occasions were labeled with sodium 13C-octanoate. Every 15 minutes, starting from just before the treatment until 4 hours after the meal, volunteers exhaled in an exetainer that was stored in the fridge for later analysis. In addition they scored their feeling of hunger, satiety and expected amount to eat on a 100 mm visual analogue scale.The 13CO2-content of the breath samples was analysed using isotope-ratio mass spectrometry. The 13CO2 excretion data were analysed by non-linear regression to allow curve fitting and calculation of the gastric half-emptying time (t½). Results: DB treatment did not alter feelings of hunger, satiation and expected amount to eat in the time frame before the meal (for all scores p .0.5). Consumption of the meal was accompanied by a rise of satiety and a decrease of hunger and expected amount to eat. Thereafter, satiety gradually decreased, while hunger and expected amount to eat increased. During the measuring period, scores for satiety were significantly higher after DB treatment as compared to placebo (AUC: 9596 ± 1293 mm*min vs. 6276 ± 1022 mm*min respectively; p,0.001). During the entire study period, volunteers felt less hungry and also the expected amount to eat was lower after DB treatment as compared to placebo [AUC hunger: 8513 ± 1186 mm*min vs. 11461 ± 1124 mm*min respectively (p ,0.01), AUC expected amount to eat: 9431 ± 950 mm*min vs. 12339 ± 969 mm*min respectively (p ,0.05)]. T1/2 between treatments was not different (103 ± 7 min for placebo vs. 100 ± 9 min for DB; p=0.7). Conclusion: Intragastric administration of the bitter receptor agonist denatonium benzoate before a meal increases satiety and delays the return of hunger up to 4 hours after the meal, although gastric emptying rate is not affected.
In Man Intragastric Administration of the Bitter Compound Denatonium Benzoate Decreases Hunger and the Occurrence of Gastric Phase III in the Fasting State Eveline Deloose, Maura Corsetti, Lukas Van Oudenhove, Inge Depoortere, Jan F. Tack Background: In mice, intragastric administration of a mixture of bitter agonists, including denatonium benzoate (DB), induced a prolonged suppression of food intake (Janssen, PNAS 2011). We recently reported a close correlation between gastric phase 3 (ph3) of the migrating motor complex (MMC) and hunger peaks (Deloose, DDW 2012).The aim of this study was to investigate the effect of DB on the occurrence of ph3 and hunger ratings in man. Methods: After an overnight fast, 11 healthy volunteers (6 men; 26±8 years; 24±2kg/m2) underwent a 36-channel antroduodenal high resolution manometry twice, with at least one week interval. Fasting motility was recorded for a full MMC cycle (2 ph3). 20 min after the occurrence of the 2nd ph3, DB (1μmol/kg) or placebo was administered intragastrically in a doubleblind randomized fashion through a nasogastric tube, to bypass the tongue. Motility recording continued until the next ph3 or 3 hrs. Subjects scored hunger every 5 min on a 10 cm visual analogue scale (VAS). Statistical analysis: A baseline hunger score was calculated by averaging VAS ratings during 10 min before administration of DB or placebo. This baseline score was subtracted from the hunger rating at each time point until 60 min after administration.The resulting delta hunger VAS scores were entered as the dependent variable in a linear mixed model analysis with time and administered agent (DB vs placebo) as continuous and categorical independent variables, respectively. The effect of interest is the interaction between time and agent, representing the difference in linear slope of the delta hunger scores between DB and placebo. Proportions were analyzed using Chi-square. Data are mean±SEM. Results: Baseline hunger scores did not differ between placebo and DB (58±9 vs 47±8 mm VAS; p=0.7). The slopes of delta hunger differed significantly between placebo and DB (time-by-agent interaction effect p=.0003, fig 1). While mean hunger ratings remained stable after administration of placebo (slope of delta hunger 0.03±0.03; p=.2), a progressive significant decrease in hunger occurred after DB (slope of delta hunger -0.11±0.03; p= .0012).The interval between baseline ph3 (98±19 vs 85±14 min; p=.8) as well as their origin (58% vs 57% gastric; p=.9) did not differ significantly between the two treatment days. During the 60 min interval after placebo, a ph3 occurred in 36% of the volunteers compared to only 11% after DB (p ,.0001). 75% of the ph3 were gastric after placebo compared to 0% after DB (p,.0001). DB was generally well tolerated, with only 1 subject reporting abdominal cramps on the night after the experiment. Conclusions: Administration of DB decreases hunger ratings and inhibits the occurrence of ph3 with a gastric origin. These data suggest potential involvement of GI bitter taste receptors in the control of hunger and interdigestive motility in man.
AGA Abstracts
S-548