Effects of intranasal oxytocin in food intake and craving: A meta-analysis of clinical trials.

OBJECTIVE: A rise of endogenous oxytocin (OT) is associated with anxiety and meal size reduction, and the effects of intranasal OT (INOT) have been examined in the management of food intake and craving. However, the discrepancy INOT effects in different disease populations are not entirely clear. RESEARCH DESIGN AND METHODS: Updated systematic review and meta-analysis. By systematically searching the PubMed, Embase and Cochrane Library, we obtained 12 controlled trials. We performed meta-analyses to examine food intake, craving, anxiety or stress reduction on INOT administration, using standard mean difference (SMD) with a 95% confidence interval (CI) and a random-effects model. RESULTS: This study examined 12 trials with 266 non-psychiatric and 157 psychiatric participants. The pooled results showed that single-dose INOT induced a significant lesser food intake in non-psychiatric subjects (SMD: -0.66 [95% CI: -1.18, -0.14]), but no effects was found in anorexia nervosa (AN) (SMD: 0.17 [95% CI: -0.32, 0.66]), bulimia nervosa (BN) and binge eating disorder (BED) (SMD: -0.41 [95% CI: -0.94, 0.11]), and schizophrenia (SMD: 0.04 [95% CI: -0.94, 1.02] subjects. Further analysis on leisure food also indicated an inhibition of consumption of chocolate biscuits in non-psychiatric subjects. Neither the non-psychiatric (SMD: -0.08 [95% CI: -0.50, 0.33]) nor the BN and BED (SMD: -0.08 [95% CI: -0.72, 0.88]) and schizophrenia subjects (SMD: -0.07 [95% CI: -1.05, 0.91]) demonstrated a difference in food craving or hunger compared with placebo. Anxiety or stress level was not influenced by INOT in any subgroup (non-psychiatric, SMD: 0.19 [95% CI: -0.22, 0.60]; AN, SMD: -0.01 [95% CI: -0.28, 0.88]; BN and BED: SMD: 0.00 [95% CI: -0.80, 0.80]). CONCLUSIONS: Single-dose INOT significantly reduces food intake in nonpsychiatric subjects, and further studies are necessary to assess the long-term effects and safety in obese patients. Whether INOT could be a treatment option for patients with eating disorders remains to be investigated.

Short-Term Protein Supplementation Does Not Alter Energy Intake, Macronutrient Intake and Appetite in 50-75 Year Old Adults.

Ageing is associated with a reduction in muscle mass and strength, termed sarcopenia. Dietary protein is important for the maintenance of muscle mass through the promotion of muscle protein synthesis. However, protein is also reported to be a highly satiating nutrient. This raises concerns that protein intake for musculoskeletal health reasons in older adults may exacerbate age-related decreased appetite and may result in reduced energy and nutrient intake. This study aimed to investigate the effect of short-term protein supplementation and its timing (morning vs. evening), on energy and nutrient intake and appetite measures in middle-older age adults. Twenty-four 50-75 year olds were recruited to a randomised cross-over trial. In phase 1 (pre-supplementation) participants completed a food diary and reported hunger and appetite on three alternate days. During the second and third phases, participants consumed a 20 g whey protein gel (78 mL/368 kJ), for four days, either in the morning (after breakfast) or the evening (before bed), whilst completing the same assessments as phase 1. No differences in dietary intakes of energy, macronutrients and micronutrients were recorded when comparing the pre-supplementation phase to the protein supplementation phases, irrespective of timing (excluding the contribution of the protein supplement itself). Similarly, no differences were observed in self-reported feelings of hunger and appetite. In conclusion, a 20 g/day whey protein supplement given outside of meal-times did not alter habitual dietary intakes, hunger or appetite in this middle-older age adult population in the short-term. This approach may be a useful strategy to increasing habitual protein intake in the middle-older age population.

Timing of chocolate intake affects hunger, substrate oxidation, and microbiota: A randomized controlled trial.

Eating chocolate in the morning or in the evening/at night, may differentially affect energy balance and impact body weight due to changes in energy intake, substrate oxidation, microbiota (composition/function), and circadian-related variables. In a randomized controlled trial, postmenopausal females (n = 19) had 100 g of chocolate in the morning (MC), in the evening/at night (EC), or no chocolate (N) for 2 weeks and ate any other food ad libitum. Our results show that 14 days of chocolate intake did not increase body weight. Chocolate consumption decreased hunger and desire for sweets (P < .005), and reduced ad libitum energy intake by ~300 kcal/day during MC and ~150 kcal/day during EC (P = .01), but did not fully compensate for the extra energy contribution of chocolate (542 kcal/day). EC increased physical activity by +6.9%, heat dissipation after meals +1.3%, and carbohydrate oxidation by +35.3% (P < .05). MC reduced fasting glucose (4.4%) and waist circumference (-1.7%) and increased lipid oxidation (+25.6%). Principal component analyses showed that both timings of chocolate intake resulted in differential microbiota profiles and function (P < .05). Heat map of wrist temperature and sleep records showed that EC induced more regular timing of sleep episodes with lower variability of sleep onset among days than MC (60 min vs 78 min; P = .028). In conclusion, having chocolate in the morning or in the evening/night results in differential effects on hunger and appetite, substrate oxidation, fasting glucose, microbiota (composition and function), and sleep and temperature rhythms. Results highlight that the "when" we eat is a relevant factor to consider in energy balance and metabolism.

The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.

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."

Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects.

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.

Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?

Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy-the two most commonly performed bariatric procedures-and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9-39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.

[Pharmacotherapy for obesity]. / Farmacotherapie voor obesitas.

Obesity is a complex endocrine disease, mainly caused by environmental, behavioral and biological factors. Maintaining weight loss is extremely difficult due to the neuro-endocrine dysregulations that stimulate the body to return to the previous, increased, weight. Identifying underlying weight-gaining factors is needed, including medication-related, psychological and endocrine factors, as well as monogenic obesity. The cornerstone of treatment is optimization of lifestyle and all other contributing factors. Achieving at least 5% weight loss already has important health benefits. If combined lifestyle intervention (CLI) alone is not successful, pharmacotherapy or bariatric surgery can be added for patients with increased weight-related health risks. Recently, novel pharmacotherapy became available, among which, liraglutide 3 mg and the combination therapy naltrexone/bupropion, which leads to an additional 5-6% mean weight loss compared to CLI alone. For rare forms of obesity there are specific drugs that target defects in the regulation of hunger and satiety. Promising new pharmacotherapy for obesity is under development.

Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties.

Cocaine not only increases brain dopamine levels but also activates the sigma1 receptor (σ1 R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D1 (D1 R), ghrelin (GHS-R1a ), and σ1 receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was assayed by measuring second messenger, cAMP and Ca2+ , levels. The effect of acute or chronic cocaine administration on receptor complex expression was assayed by in situ proximity ligation assay. In silico procedures were used for molecular model building. σ1 R KO mice were used for confirming involvement of this receptor. Upon identification of protomer interaction and receptor functionality, a unique structural model for the macromolecular complex formed by σ1 R, D1 R, and GHS-R1a is proposed. The functionality of the complex, able to couple to both Gs and Gq proteins, is affected by cocaine binding to the σ1 R, as confirmed using samples from σ1 R-/- mice. The expression of the macromolecular complex was differentially affected upon acute and chronic cocaine administration to rats. The constructed 3D model is consistent with biochemical, biophysical, and available structural data. The σ1 R, D1 R, and GHS-R1a complex constitutes a functional unit that is altered upon cocaine binding to the σ1 R. Remarkably, the heteromer can simultaneously couple to two G proteins, thus allowing dopamine to signal via Ca2+ and ghrelin via cAMP. The anorexic action of cocaine is mediated by such complex whose expression is higher after acute than after chronic administration regimens.

Effect of oral or intragastric delivery of the bitter tastant quinine on food intake and appetite sensations: a randomised crossover trial.

Stimulation of gastrointestinal taste receptors affects eating behaviour. Intraduodenal infusion of tastants leads to increased satiation and reduced food intake, whereas intraileal infusion of tastants does not affect eating behaviour. Currently, it is unknown whether oral- or intragastric administration of tastants induces a larger effect on eating behaviour. This study investigated the effects of oral- and/or intragastric administration of quinine on food intake, appetite sensations and heart rate variability (HRV). In a blinded randomised crossover trial, thirty-two healthy volunteers participated in four interventions with a 1-week washout: oral placebo and intragastric placebo (OPGP), oral quinine and intragastric placebo (OQGP), oral placebo and intragastric quinine (OPGQ) and oral quinine and intragastric quinine (OQGQ). On test days, 150 min after a standardised breakfast, subjects ingested a capsule containing quinine or placebo and were sham-fed a mixture of quinine or placebo orally. At 50 min after intervention, subjects received an ad libitum meal to measure food intake. Visual analogue scales for appetite sensations were collected, and HRV measurements were performed at regular intervals. Oral and/or intragastric delivery of the bitter tastant quinine did not affect food intake (OPGP: 3273·6 (sem 131·8) kJ, OQGP: 3072·7 (sem 132·2) kJ, OPGQ: 3289·0 (sem 132·6) kJ and OQGQ: 3204·1 (sem 133·1) kJ, P = 0·069). Desire to eat and hunger decreased after OQGP and OPGQ compared with OPGP (P < 0·001 and P < 0·05, respectively), whereas satiation, fullness and HRV did not differ between interventions. In conclusion, sole oral sham feeding with and sole intragastric delivery of quinine decreased desire to eat and hunger, without affecting food intake, satiation, fullness or HRV.

Exploring Patterns of Disturbed Eating in Psychosis: A Scoping Review.

Disturbed eating behaviours have been widely reported in psychotic disorders since the early 19th century. There is also evidence that antipsychotic (AP) treatment may induce binge eating or other related compulsive eating behaviours. It is therefore possible that abnormal eating patterns may contribute to the significant weight gain and other metabolic disturbances observed in patients with psychosis. In this scoping review, we aimed to explore the underlying psychopathological and neurobiological mechanisms of disrupted eating behaviours in psychosis spectrum disorders and the role of APs in this relationship. A systematic search identified 35 studies that met our eligibility criteria and were included in our qualitative synthesis. Synthesizing evidence from self-report questionnaires and food surveys, we found that patients with psychosis exhibit increased appetite and craving for fatty food, as well as increased caloric intake and snacking, which may be associated with increased disinhibition. Limited evidence from neuroimaging studies suggested that AP-naïve first episode patients exhibit similar neural processing of food to healthy controls, while chronic AP exposure may lead to decreased activity in satiety areas and increased activity in areas associated with reward anticipation. Overall, this review supports the notion that AP use can lead to disturbed eating patterns in patients, which may contribute to AP-induced weight gain. However, intrinsic illness-related effects on eating behaviors remain less well elucidated, and many confounding factors as well as variability in study designs limits interpretation of existing literature in this field and precludes firm conclusions from being made.

Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial.

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.

Effects of opioid receptor ligands in rats trained to discriminate 22 from 2 hours of food deprivation suggest a lack of opioid involvement in eating for hunger.

It is well accepted that opioids promote feeding for reward. Some studies suggest a potential involvement in hunger-driven intake, but they suffer from the scarcity of methodologies differentiating between factors that intersect eating for pleasure versus energy. Here, we used a unique food deprivation discrimination paradigm to test a hypothesis that, since opioids appear to control feeding reward, injection of opioid agonists would not produce effects akin to 22 h of food deprivation. We trained rats to discriminate between 22 h and 2 h food deprivation in a two-lever, operant discrimination procedure. We tested whether opioid agonists at orexigenic doses produce discriminative stimulus effects similar to 22 h deprivation. We injected DAMGO, DSLET, or orphanin FQ in the paraventricular hypothalamic nucleus (PVN), a site regulating hunger/satiety, and butorphanol subcutaneously (to produce maximum consumption). We assessed the ability of the opioid antagonist, naltrexone, to reduce the discriminative stimulus effects of 22 h deprivation and of the 22 h deprivation-like discriminative stimulus effects of PVN-injected hunger mediator, neuropeptide Y (NPY). In contrast to PVN NPY, centrally or peripherally injected opioid agonists failed to induce discriminative stimuli similar to those of 22 h deprivation. In line with that, naltrexone did not reduce the hunger discriminative stimuli induced by either 22 h deprivation or NPY administration in 2 h food-restricted subjects, even though doses used therein were sufficient to decrease deprivation-induced feeding in a non-operant setting in animals familiar with consequences of 2 h and 22 h deprivation. We conclude that opioids promote feeding for reward rather than in order to replenish lacking energy.

Dairy products influence gut hormone secretion and appetite differently: A randomized controlled crossover trial.

Little is known about how dairy products with different nutrient contents and food matrices affect appetite sensation and gut hormone secretion. The objective of this study was to investigate how appetite sensation and gut hormone secretion in healthy adults are affected by meals with the same amount of fat but from different dairy products. Forty-seven healthy adults (70% women) were recruited to a randomized controlled crossover study with 4 dairy meals consisting of butter, cheese, whipped cream, or sour cream, corresponding to 45 g (approximately 60 energy percent) of fat. Plasma samples were collected for analysis of cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY), and ghrelin concentrations at 0, 2, 4, and 6 h after the meals and analyzed as the incremental area under the curve (iAUC0-6h) in a mixed model. Hunger, satiety, and appetite sensations were measured with a visual analog scale (VAS) immediately after finishing the meals and at 4 and 6 h postprandially. Intake of cheese induced a higher level of plasma PP-iAUC0-6h compared with butter or whipped cream, and a higher level of plasma CCK-iAUC0-6h compared with whipped cream. Intake of whipped cream increased VAS appetite at 4 h compared with cheese or sour cream, and at 6 h compared with cheese or butter. No significant meal effect was found for hunger, satiety, plasma PYY, or plasma ghrelin concentration. Intake of cheese increased postprandial plasma PP and CCK concentrations and decreased appetite compared with whipped cream but not with sour cream. These findings encourage further investigations of how different dairy products affect gut hormone secretion and appetite sensation.

New Zealand Bitter Hops Extract Reduces Hunger During a 24 h Water Only Fast.

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.

Effect of Macronutrient Type and Gastrointestinal Release Site on PYY Response in Normal Healthy Subjects.

BACKGROUND AND AIMS: Enteroendocrine L cells release satiety inducing hormones in response to stimulation by luminal macronutrients. We sought to profile the differential effect of macronutrient type and site of release on circulating concentrations of the L cell-derived enteroendocrine hormone peptide tyrosine tyrosine (amino acids 1 to 36) (PYY). MATERIALS AND METHODS: Eight healthy volunteers were recruited to a randomized, double-blinded, six-way crossover study. At each visit, the participants consumed a 500-kcal drink containing carbohydrate, protein, or fat in either gastric or small intestinal release formulations. Plasma PYY concentrations and hunger ratings were assessed for 3 hours after consumption of the test drink. The food intake was recorded thereafter at an ad libitum lunch. RESULTS: Microcapsular formulations targeting the distal small intestinal delivery of fat, but not carbohydrate or protein, markedly enhance PYY release relative to macronutrient delivery in gastric release formulations. Food intake at an ad libitum meal was lowest after consumption of the formulation releasing fat at the distal small intestine. CONCLUSION: Targeting of fat to the distal small intestine in delayed release microcapsules enhanced PYY release and was associated with reductions in food intake.

Effects of liraglutide plus phentermine in adults with obesity following 1 year of treatment by liraglutide alone: A randomized placebo-controlled pilot trial.

BACKGROUND: This pilot study evaluated whether adding phentermine to liraglutide would induce further weight loss in participants who had previously lost weight with liraglutide alone. SUBJECTS/METHODS: Participants were 45 adults with obesity (75.6% female, 55.6% white, body mass index = 34.3 ±â€¯4.7 kg/m2) who had lost an average of 12.6 ±â€¯6.8% of initial weight during a prior 1-year randomized trial with liraglutide and intensive behavioral treatment. Participants were re-randomized, in a double-blinded fashion, to liraglutide 3.0 mg plus phentermine 15.0 mg (liraglutide-phentermine) or liraglutide plus placebo (liraglutide-placebo). Participants also were provided with four, 15-minute counseling sessions during the 12-week extension study. RESULTS: At week 12, the liraglutide-phentermine and liraglutide-placebo groups lost a mean (±SEM) of 1.6 ±â€¯0.6% and 0.1 ±â€¯0.5% of re-randomization weight, respectively (p = 0.073). Two (9.1%) liraglutide-phentermine participants and one (4.3%) liraglutide-placebo participant lost ≥5% of re-randomization weight; 19 (86.4%) and 16 (69.9%) participants, respectively, maintained their full weight loss achieved in the prior 1-year trial (p = 0.125). Liraglutide-phentermine participants generally reported larger reductions in hunger and food preoccupation than liraglutide-placebo participants during the first 8 weeks of the extension study. CONCLUSIONS: The combination of liraglutide and phentermine appeared to be well-tolerated but did not produce additional clinically meaningful weight loss in individuals who had already lost 12.6% of initial weight with liraglutide alone. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02911818.

The effects of whey and soy liquid breakfast on appetite response, energy metabolism, and subsequent energy intake.

OBJECTIVES: The aim of this study was to examine the effects of animal-based protein (whey; WP) compared with plant-based protein (soy; SP) and carbohydrate (CHO) liquid breakfast on appetite, energy metabolism, and subsequent energy intake. METHODS: Seventeen healthy individuals consumed three isocaloric breakfast smoothies with whey, soy, or carbohydrate (no protein) in a double-blind, randomized crossover design. Participants completed an 11-point rating scale of appetite profile (before, 0, 60, 120, and 180 min). Indirect calorimetry was used to determine the thermic effect of a meal (TEM; at 45-60, 105-120, and 165-180 min). An ad libitum lunch was offered at 180 min after breakfast and energy intake was assessed. RESULTS: There was a significant difference in hunger (P = 0.033), fullness (P = 0.002), satiety (P = 0.001), desire to eat (P = 0.024), and prospective food consumption (P = 0.021) between the three breakfast meals. Fullness and SP compared with CHO. A higher (P < 0.001) TEM and lower (P < 0.05) respiratory exchange ratio (RER) was observed after WP and SP compared with CHO. In addition, a higher (P = 0.022) energy intake at lunch was observed after CHO (769 ± 259 kcal) compared with WP (654 ± 252 kcal) and SP (664 ± 296 kcal), with no difference (P = 0.966) between WP and SP. Consuming SP at breakfast exerts comparable effects to WP on appetite profile, energy metabolism, and subsequent energy intake, suggesting that SP is a reasonable alternative to WP as a protein supplement source to aid in body weight control.

Motilin: from gastric motility stimulation to hunger signalling.

After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution - with the use of knockout models - sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease. Luminal stimuli, such as bitter tastants, have been identified as modulators of motilin release, with effects on hunger and food intake. The current state of knowledge and potential implications for therapy are summarized in this Review.

Ghrelin's effects on food motivation in rats are not limited to palatable foods.

The "hunger" hormone, ghrelin, is powerfully orexigenic. Even in the absence of hunger, ghrelin delivery to rats increases consumption of chow, as well as palatable foods, and increases motivated behaviour for palatable food rewards. Inspired by the finding that ghrelin increases the selection of chow in rats offered a choice diet (lard, sucrose or chow) and even in rats bingeing on a high-fat diet, we aimed to explore whether the effects of ghrelin on motivation extend to regular chow. Rats were conditioned to lever press for either chow or sucrose pellets in a progressive ratio (PR) operant conditioning task. The effect of acute i.c.v. delivery of ghrelin on both chow and sucrose self-administration was determined and compared with overnight fasting (ie, when endogenous ghrelin levels are elevated). We found that ghrelin similarly increased motivated behaviour for chow and sucrose pellets. The effect of fasting on motivated behaviour for both food pellets was comparable in magnitude to that induced by ghrelin, albeit with an earlier ceiling effect during the PR session. Devaluation experiments (in which rats are offered either food reinforcer in excess prior to PR testing) did not support the hypothesis that sucrose pellets would be more difficult to devalue (as a result of their higher incentive value) than chow pellets. When exchanging the respective pellets during a PR session, chow-conditioned rats were more motivated for sucrose pellets compared to chow pellets; however, sucrose-conditioned rats were similarly motivated for chow pellets compared to sucrose pellets. Thus, using sucrose as a reward may increase the motivation even for less palatable foods. We conclude that the impact of ghrelin on food-motivated behaviour in fed rats is not limited to palatable foods but extends to regular chow, and also that the magnitude of the effect is considerable compared to that of an overnight fast.

Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment.

AIM: Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52 weeks of treatment. METHODS: A prospective study with measurements at baseline and at >150 weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal. RESULTS: Hunger rated on visual analog scales at 120 min after the meal significantly decreased from 46 ±â€¯10 mm at baseline to 17 ±â€¯6 mm at long-term assessment. Furthermore, satiety at 5 and 120 min after the meal significantly increased from baseline to long-term assessment (5 min: 70 ±â€¯7 mm to 87 ±â€¯3 mm; 120 min: 43 ±â€¯10 mm to 79 ±â€¯8 mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2 ±â€¯0.2 at baseline to 2.6 ±â€¯1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6 ±â€¯4.8 and 11.4 ±â€¯2.2, respectively) to long-term assessment (14.0 ±â€¯2.1 and 10.0 ±â€¯1.9). CONCLUSION: First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.