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The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.
Verbeure, W, Deloose, E, Tóth, J, Rehfeld, JF, Van Oudenhove, L, Depoortere, I, Tack, J
American journal of physiology. Endocrinology and metabolism. 2021;(1):E1-E10
Abstract
Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg), or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min before administration and every 10 min after administration for a period of 2 h. Hunger was rated at the same time points on a visual analogue scale. ID bitter administration did not affect hunger sensations, motilin, or acyl-ghrelin release compared with its placebo infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50 and 70 min after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 min before food intake.NEW & NOTEWORTHY Bitter tastants are a potential new weight-loss treatment. This is a noninvasive, easy approach, which should be received with considerable enthusiasm by the public. However, literature about bitter administration lacks consistency in methods and findings. We summarize how the compound should be given based on: the site of administration, the best bitter compound to use, and at what timing in respect to the meal. This paper is therefore a fundamental step to continue research toward the further development of the "bitter pill."
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Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial.
Tronieri, JS, Wadden, TA, Walsh, O, Berkowitz, RI, Alamuddin, N, Gruber, K, Leonard, S, Bakizada, ZM, Chao, AM
International journal of obesity (2005). 2020;(2):353-361
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Abstract
BACKGROUND Some weight loss medications, including liraglutide 3.0 mg, are thought to facilitate weight loss by improving appetite control. However, no studies have evaluated their long-term appetitive effects. SUBJECTS/METHODS This study examined changes in appetite in a subsample of 113 adults with obesity (76.1% female, 55.8% white, BMI = 38.8 ± 4.8 kg/m2) who participated in a 52-week trial. Participants were randomized to intensive behavioral therapy alone (IBT-alone), IBT with liraglutide 3.0 mg/day (IBT-liraglutide), or IBT-liraglutide combined with a 12-week meal replacement diet (Multi-component). Participants rated their hunger, fullness after meals, liking of meals, and food preoccupation (all as experienced over the past week) using visual analogue scales (0-100 mm). Ratings were completed at baseline and eight subsequent visits over the year. RESULTS At week 52, participants treated by IBT-alone lost 6.2 ± 1.6% of baseline weight, compared with 11.8 ± 1.6% and 12.1 ± 1.5% in the IBT-liraglutide and Multi-component groups, respectively. Compared to IBT-alone, IBT-liraglutide participants reported larger reductions at week 6 in hunger (-0.3 ± 4.2 vs -16.8 ± 4.0 mm, p = .005) and food preoccupation (+0.2 ± 3.7 vs -16.3 ± 3.6 mm, p = .002) and larger increases in fullness (-5.1 ± 3.2 vs +9.8 ± 3.0 mm, p = .001). These significant differences persisted at all assessments through week 24. There were no differences between IBT-alone and IBT-liraglutide in meal liking. IBT-alone and Multi-component participants differed in hunger at week 6, and in food preoccupation at all assessments through week 24. Multi-component participants reported reduced liking of meals relative to the IBT-alone and IBT-liraglutide groups through weeks 40 and 52, respectively. There were no other differences among any groups at week 52. CONCLUSIONS Consistent with short-term studies, IBT-liraglutide participants reported greater improvements in hunger, fullness, and food preoccupation than those assigned to IBT-alone. Differences in appetite persisted for 24 weeks but were not maintained at week 52, despite the relatively greater weight losses in the liraglutide-treated participants at the trial's end.
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Changes in weight control behaviors and hedonic hunger in a commercial weight management program adapted for individuals with type 2 diabetes.
Schulte, EM, Tuerk, PW, Wadden, TA, Garvey, WT, Weiss, D, Hermayer, KL, Aronne, LJ, Becker, LE, Fujioka, K, Miller-Kovach, K, et al
International journal of obesity (2005). 2020;(5):990-998
Abstract
BACKGROUND A WW (formerly Weight Watchers) program adapted for persons with type 2 diabetes mellitus (T2DM) previously was found to be more effective than standard care (SC) intervention for weight loss, improved glycemic control, and weight- and diabetes-related quality of life measures. With data from the same national trial, this study examined whether WW adapted for persons with T2DM also increased engagement in weight control behaviors and decreased hedonic hunger, each of which could contribute to improved diabetes management. INTERVENTION AND METHODS Individuals with T2DM (n = 563) and overweight or obesity participated in a 12-month, 16-site, randomized trial of WW with diabetes counseling or SC. Hierarchical linear modeling (HLM) evaluated whether 12-month changes in weight control behaviors (Eating Behavior Inventory; EBI) and hedonic hunger (Power of Food Scale; PFS) differed by treatment condition. If a significant treatment effect was found, 12-month changes in EBI/PFS were regressed on 12-month changes in HbA1c and percent weight loss to explore potential treatment differences in these associations. RESULTS EBI scores increased significantly over the 12-months (p < 0.001), with greater improvements in WW than SC (p < 0.001). PFS decreased significantly in the 12-months (p < 0.001), with no differences between treatment groups (p = 0.15). HLM analyses that followed up on the significant treatment effect for 12-month change in EBI revealed no significant differences by treatment condition for the relationship between change in EBI scores and change in HbA1c (p = 0.14) or percent weight loss (p = 0.32). Across all participants, 12-month improvements in EBI and PFS were related to improved HbA1c (r = 0.22; -0.13, respectively) and greater percent weight loss (r = 0.41; -0.18, respectively) (ps < 0.01). CONCLUSIONS WW with diabetes counseling produced greater engagement in weight control behaviors in those with T2DM than did SC. Across both groups, improved weight control behaviors and hedonic hunger were related to improved glycemic control and weight loss.
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Appetite Control across the Lifecourse: The Acute Impact of Breakfast Drink Quantity and Protein Content. The Full4Health Project.
Crabtree, DR, Buosi, W, Fyfe, CL, Horgan, GW, Manios, Y, Androutsos, O, Giannopoulou, A, Finlayson, G, Beaulieu, K, Meek, CL, et al
Nutrients. 2020;(12)
Abstract
Understanding the mechanisms of hunger, satiety and how nutrients affect appetite control is important for successful weight management across the lifecourse. The primary aim of this study was to describe acute appetite control across the lifecourse, comparing age groups (children, adolescents, adults, elderly), weight categories, genders and European sites (Scotland and Greece). Participants (n = 391) consumed four test drinks, varying in composition (15% (normal protein, NP) and 30% (high protein, HP) of energy from protein) and quantity (based on 100% basal metabolic rate (BMR) and 140% BMR), on four separate days in a double-blind randomized controlled study. Ad libitum energy intake (EI), subjective appetite and biomarkers of appetite and metabolism (adults and elderly only) were measured. The adults' appetite was significantly greater than that of the elderly across all drink types (p < 0.004) and in response to drink quantities (p < 0.001). There were no significant differences in EI between age groups, weight categories, genders or sites. Concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were significantly greater in the elderly than the adults (p < 0.001). Ghrelin and fasting leptin concentrations differed significantly between weight categories, genders and sites (p < 0.05), while GLP-1 and PYY concentrations differed significantly between genders only (p < 0.05). Compared to NP drinks, HP drinks significantly increased postprandial GLP-1 and PYY (p < 0.001). Advanced age was concomitant with reduced appetite and elevated anorectic hormone release, which may contribute to the development of malnutrition. In addition, appetite hormone concentrations differed between weight categories, genders and geographical locations.
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Virtual grocery shopping and cookie consumption following intranasal insulin or placebo application.
Rodriguez-Raecke, R, Sommer, M, Brünner, YF, Müschenich, FS, Sijben, R
Experimental and clinical psychopharmacology. 2020;(4):495-500
Abstract
Insulin receptors are present in brain areas that are involved in the control of hunger and satiety, and intranasal insulin is assumed to have an anorexigenic effect. This known influence of insulin on satiety encouraged us to investigate the effect of intranasal insulin on feeding-related behaviors. The aim of the current study was to explore the influence of 40 IU of intranasal insulin on the grocery shopping behavior and cookie consumption in a group of 30 healthy young men, using a crossover randomized double-blind design. Using a virtual mock supermarket, we tested whether the intranasal administration of insulin influences purchase behavior in comparison to a placebo or control condition. The participants also provided hedonic ratings of food pictures, as well as their subjective feeling of hunger. We calculated an objective measure of hunger from the amount of cookies eaten. In contradiction to our hypotheses, no significant differences regarding ratings, calorie content of purchased food products, and cookie consumption were found between the treatment conditions. Our conclusion is that 40 IU intranasal insulin had no influence on the evaluation of pictured foods in healthy young men in our task. Acknowledging that previous studies have found effects for intranasal insulin and food cue processing, we suggest that future research should focus on chemosensory stimulation or cognitive tasks in behavioral experiments and carefully consider the doses of intranasal insulin. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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New Zealand Bitter Hops Extract Reduces Hunger During a 24 h Water Only Fast.
Walker, E, Lo, K, Tham, S, Pahl, M, Lomiwes, D, Cooney, J, Wohlers, M, Gopal, P
Nutrients. 2019;(11)
Abstract
Intermittent fasting improves metabolic and cardiac health. However, increased hunger towards the end of the fasting period may affect compliance and limit its application. Our aim was to determine the effect of anorexigenic agent co-therapy on subjective ratings of appetite during the 16-24 h period of a day-long water-only intermittent fast. Thirty adult men were recruited and required to fast for 24 h from 18:00 h to 18:00 h on the same day of the week for three subsequent weeks. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 100 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. From 18-24 h of the 24 h fast, both the HD and LD treatment groups exhibited a statistically significant (p < 0.05) > 10% reduction in hunger. Additionally, the expected lunchtime increase in hunger that was present in the placebo group (12:00 h) was absent in both the HD and LD groups. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during intermittent fasting, and show that bitter compounds may regulate appetite independently of meal timing.
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Subjective Hunger, Gastric Upset, and Sleepiness in Response to Altered Meal Timing during Simulated Shiftwork.
Gupta, CC, Centofanti, S, Dorrian, J, Coates, AM, Stepien, JM, Kennaway, D, Wittert, G, Heilbronn, L, Catcheside, P, Noakes, M, et al
Nutrients. 2019;(6)
Abstract
Shiftworkers report eating during the night when the body is primed to sleep. This study investigated the impact of altering food timing on subjective responses. Healthy participants (n = 44, 26 male, age Mean ± SD = 25.0 ± 2.9 years, BMI = 23.82 ± 2.59kg/m2) participated in a 7-day simulated shiftwork protocol. Participants were randomly allocated to one of three eating conditions. At 00:30, participants consumed a meal comprising 30% of 24 h energy intake (Meal condition; n = 14, 8 males), a snack comprising 10% of 24 h energy intake (Snack condition; n = 14; 8 males) or did not eat during the night (No Eating condition; n = 16, 10 males). Total 24 h individual energy intake and macronutrient content was constant across conditions. During the night, participants reported hunger, gut reaction, and sleepiness levels at 21:00, 23:30, 2:30, and 5:00. Mixed model analyses revealed that the snack condition reported significantly more hunger than the meal group (p < 0.001) with the no eating at night group reporting the greatest hunger (p < 0.001). There was no difference in desire to eat between meal and snack groups. Participants reported less sleepiness after the snack compared to after the meal (p < 0.001) or when not eating during the night (p < 0.001). Gastric upset did not differ between conditions. A snack during the nightshift could alleviate hunger during the nightshift without causing fullness or increased sleepiness.
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Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomy.
Li, G, Ji, G, Hu, Y, Liu, L, Jin, Q, Zhang, W, Liu, L, Wang, Y, Zhao, J, von Deneen, KM, et al
Psychoneuroendocrinology. 2019;:229-236
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Abstract
The "hunger" hormone ghrelin regulates food-intake and preference for high-calorie (HC) food through modulation of the mesocortico-limbic dopaminergic pathway. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat morbid obesity. We tested the hypothesis that LSG-induced reductions in appetite and total ghrelin levels in blood are associated with reduced prefrontal brain reactivity to food cues. A functional magnetic resonance imaging (fMRI) cue-reactivity task with HC and low-calorie (LC) food pictures was used to investigate brain reactivity in 22 obese participants tested before and one month after bariatric surgery (BS). Nineteen obese controls (Ctr) without surgery were also tested at baseline and one-month later. LSG significantly decreased (1) fasting plasma concentrations of total ghrelin, leptin and insulin, (2) craving for HC food, and (3) brain activation in the right dorsolateral prefrontal cortex (DLPFC) in response to HC vs. LC food cues (PFWE < 0.05). LSG-induced reduction in DLPFC activation to food cues were positively correlated with reduction in ghrelin levels and reduction in craving ratings for food. Psychophysiological interaction (PPI) connectivity analyses showed that the right DLPFC had stronger connectivity with the ventral anterior cingulate cortex (vACC) after LSG, and changes in BMI were negatively correlated with changes in connectivity between the right DLPFC and vACC in the LSG group only. These findings suggest that LSG-induced weight-loss may be related to reductions in ghrelin, possibly leading to decreased food craving and hypothetically reducing DLPFC response to the HC food cues.
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Is hunger important to model in fMRI visual food-cue reactivity paradigms in adults with obesity and how should this be done?
Chin, SH, Kahathuduwa, CN, Stearns, MB, Davis, T, Binks, M
Appetite. 2018;:388-397
Abstract
We considered 1) influence of self-reported hunger in behavioral and fMRI food-cue reactivity (fMRI-FCR) 2) optimal methods to model this. Adults (N = 32; 19-60 years; F = 21; BMI 30-39.9 kg/m2) participated in an fMRI-FCR task that required rating 240 images of food and matched objects for 'appeal'. Hunger, satiety, thirst, fullness and emptiness were measured pre- and post-scan (visual analogue scales). Hunger, satiety, fullness and emptiness were combined to form a latent factor (appetite). Post-vs. pre-scores were compared using paired t-tests. In mixed-effects models, appeal/fMRI-FCR responses were regressed on image (i.e. food/objects), with random intercepts and slopes of image for functional runs nested within subjects. Each of hunger, satiety, thirst, fullness, emptiness and appetite were added as covariates in 4 forms (separate models): 1) change; 2) post- and pre-mean; 3) pre-; 4) change and pre-. Satiety decreased (Δ = -13.39, p = 0.001) and thirst increased (Δ = 11.78, p = 0.006) during the scan. Changes in other constructs were not significant (p's > 0.05). Including covariates did not influence food vs. object contrast of appeal ratings/fMRI-FCR. Significant image X covariate interactions were observed in some fMRI models. However, including these constructs did not improve the overall model fit. While some subjective, self-reported hunger, satiety and related constructs may be moderating fMRI-FCR, these constructs do not appear to be salient influences on appeal/fMRI-FCR in people with obesity undergoing fMRI.
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Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A randomised trial.
Sim, AY, Lim, EX, Leow, MK, Cheon, BK
Psychoneuroendocrinology. 2018;:103-112
Abstract
Recent evidence suggests that lower perceived socioeconomic status is linked to increased appetite and intake of greater calories. Yet, whether insecurity of socioeconomic resources directly influences regulatory systems of appetite and energy intake is not known. Considering psychological states, mindsets and beliefs have shown to meaningfully affect physiological responses to food, the present study tested the hypothesis that low subjective socioeconomic status (SSS) will have a direct influence on physiological responses, such as appetite-related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight healthy males were randomly (crossover, counterbalanced) assigned, to two experimental conditions where participants were either experimentally induced to feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase in active ghrelin (an orexigenic hormone) following the SSS manipulation compared with baseline, while no change in active ghrelin was observed in CON. Furthermore, participants reported lower fullness and satiety following low SSS compared with CON. Our findings demonstrate that SSS may influence hunger regulation and appetite, and suggest that physiological systems regulating energy balance (i.e. caloric resources) may also be sensitive to perceived deprivation or imbalances in critical non-food resources (socioeconomic resources).