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Obese people are mostly unable to maintain successful weight loss after the end of a dietary change. One reason is that conventional weight reduction concepts neglect physiological hunger and satiety perception, leading to a relapse to previous eating habits on the long run. We examined the long-term efficacy of a psychological smartphone weight loss program, which avoids any dietary instructions and aims at relearning of satiety perception. Parameters of body weight alterations and psychological features, for example, satiety perception, food cravings, and emotional eating, were explored in a nonrandomized experimental study comprising 75 obese participants. Measurements occurred at baseline, two times during program application, as well as at 6- and 12-month follow-up. Participants displayed significant weight loss during the entire study period (p = .029) and showed an improved body composition at the 6-month follow-up (p = .018). These effects were associated with increased satiety perception, as well as reduced food cravings, and emotional eating habits. Notably, all improvements in measured parameters significantly sustained between the end of the program and the 12-month follow-up (p < .005 for all). Psychological relearning of satiety perception may outclass dietary approaches in terms of long-term efficiency., (© 2024 The Author(s). Applied Psychology: Health and Well‐Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

The gut-brain axis plays a pivotal role in the finely tuned orchestration of food intake, where both homeostatic and hedonic processes collaboratively control our dietary decisions. This interplay involves the transmission of mechanical and chemical signals from the gastrointestinal tract to the appetite centers in the brain, conveying information on meal arrival, quantity, and chemical composition. These signals are processed in the brain eventually leading to the sensation of satiety and the termination of a meal. However, the regulation of food intake and appetite extends beyond the realms of pure physiological need. Hedonic mechanisms, including sensory perception (i.e., through sight, smell, and taste), habitual behaviors, and psychological factors, exert profound influences on food intake. Drawing from studies in animal models and human research, this comprehensive review summarizes the physiological mechanisms that underlie the gut-brain axis and its interplay with the reward network in the regulation of appetite and satiety. The recent advancements in neuroimaging techniques, with a focus on human studies that enable investigation of the neural mechanisms underpinning appetite regulation are discussed. Furthermore, this review explores therapeutic/pharmacological strategies that hold the potential for controlling food intake., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive. Our understanding of the roles these bioregulators play has benefited from modern behavioral analyses, which have improved the time resolution of intake measures, allowing for attention to the details of the patterns within a bout of intake. This has led to behavioral interpretation in ways that are helpful in understanding the many controls of water intake and has expanded our understanding beyond the dichotomy that something which increases water intake is simply a "stimulator" while something that decreases water intake is simply a "satiety" factor. Synthesizing the available information, we describe a framework in which thirst is driven directly by perturbations in fluid intake and indirectly modified by several bioregulators. This allows us to better highlight areas that are in need of additional attention to form a more comprehensive understanding of how the system transitions between states of thirst and satiety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Limited evidence is available about the variability of appetitive responses within individuals after an acute bout of exercise. The present study aimed to assess the consistency and individual variability of post-exercise appetitive responses in healthy individuals. Twenty participants (10 females, 23.9 ± 4.1 years, 22.5 ± 2.0 kg m -2 ) joined the laboratory to perform four sessions separated by a minimum of 5 days: i) a control session with a rest period before and an ad libitum lunch (REST), and ii) three identical exercise sessions (EX) with a 30-min moderate-intensity (60-70% of predicted maximal heart rate) walking bout ending 25 min before the ad libitum lunch. Subjective appetite sensations were assessed before and after the meal at regular intervals, and satiety quotients were calculated. Food reward was assessed by the Leeds Food Preference Questionnaire before and after lunch. For each EX session, the difference with the REST session was calculated (Δ = EX - REST). Energy and macronutrient intake were consistent in response to exercise (all intraclass correlation coefficients (ICC) > 0.8) while results showed that post-exercise subjective appetite sensations and satiety quotients varied across the three EX sessions (almost all ICC < 0.7). Food reward was overall consistent in response to exercise before the test meal but not after. When considering the changes (Δ), the results showed no or poor consistency for most of the appetitive outcomes. To conclude, energy and macronutrient intake, as well as pre-meal food reward, are consistent after exercise in healthy individuals, while subjective appetite sensations are not stable within individuals across the sessions. Regarding the variations from REST to EX sessions, the results suggest that the individual changes observed are only random day-to-day variations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Terminating a meal after achieving satiation is a critical step in maintaining a healthy energy balance. Despite the extensive collection of information over the last few decades regarding the neural mechanisms controlling overall eating, the mechanism underlying different temporal phases of eating behaviors, especially satiation, remains incompletely understood and is typically embedded in studies that measure the total amount of food intake. In this review, we summarize the neural circuits that detect and integrate satiation signals to suppress appetite, from interoceptive sensory inputs to the final motor outputs. Due to the well-established role of cholecystokinin (CCK) in regulating the satiation, we focus on the neural circuits that are involved in regulating the satiation effect caused by CCK. We also discuss several general principles of how these neural circuits control satiation, as well as the limitations of our current understanding of the circuits function. With the application of new techniques involving sophisticated cell-type-specific manipulation and mapping, as well as real-time recordings, it is now possible to gain a better understanding of the mechanisms specifically underlying satiation., Competing Interests: Declaration of competing interest No competing interests of any authors or persons related to this research are declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Memory processes may contribute to appetite regulation. When people look at palatable foods, their desire to consume them depends upon memory retrieval (i.e., recalling if it will taste good). If memory inhibition occurs during satiety, then pleasant eating-related memories will not be retrieved, making eating less likely. In contrast, if memory inhibition is less efficient, pleasant food-related memories will be retrieved, the food will appear desirable, and the chance of consumption increases. Here we tested whether a putative measure of memory inhibition could predict post-meal snack food intake. Study participants looked at palatable snacks and judged their desire to eat them (i.e., a memory-dependent process), and then ate a small sample of each food, and rated them for liking (i.e., an orosensory-dependent process) - all using category rating scales. Following a filling meal, this test was repeated, alongside others. Finally, participants were given the opportunity for ad libitum snack food consumption, in addition to collecting measures such as impulsivity. Poorer memory inhibition (i.e., smaller changes in wanting relative to liking from pre-to post-meal) was associated with greater consumption of snacks on the ad libitum test (Sr 2 % = 4.4, p = 0.006) after controlling for other variables likely to influence eating (e.g., impulsivity). This effect was maintained even when the memory inhibition measure was based on foods different to those being consumed on the ad libitum snacking test. In conclusion, memory inhibition may contribute to food intake regulation, and when this is less efficient, more palatable food is likely to be eaten in the post-meal period., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We investigated the effects of complex textural attributes of food i.e. lubricity and oral coating, on appetite ratings, food intake, salivary and gut peptides for the first time. Milk protein-rich beverages (whey and casein) were instrumentally analyzed (tribology, viscosity and adsorption, latter representing oral coating) using in vitro measurements. Then these protein beverage preloads differing in their coating properties (low coating, medium coating and high coating) were assessed in two cross-over satiety trials (Study 1, n=37; Study 2, n=15; Total n= 52). Fullness ratings increased in the high coating beverage condition (p < .05) only after 20 min with limited effects on other time points, suggesting a sporadic effect of oral coating on appetite ratings (n=37). There was a correlation between concentration of protein in saliva and appetite ratings; the higher the concentration of protein in saliva the lower the desire to eat (r = - 0.963; p < 0.05) and prospective food consumption ratings (r =- 0.980; p < 0.05). Human saliva was more lubricating after ingesting preload with high coating properties, thus explaining the results on appetite ratings. There was no effect of oral coating on energy intake and gut peptides (n=15), suggesting that complex textural attributes having influence on oral processing might not have any effect on the later parts of the satiety cascade. Oral coating/ lubricity appears to have a subtle and sporadic effect on appetite suppression, which needs further investigation with changing macronutrients/energy load and degree of coating/ lubricity., Competing Interests: Declaration of competing interest There are no known conflicts of interest associated with this publication., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The current study aimed to evaluate the effect different modalities (pictures and words) of food stimuli have on inhibitory control under different homeostatic states. To this end, the homeostatic state was altered by asking participants to fast for 16 h ( n = 67) or eat lunch as usual ( n = 76) before completing an online stop-signal task with modal (pictures) and amodal (words) food and valenced-matched non-food stimuli. The inclusion of non-food stimuli allowed us to test the food specificity of the effect. We found a significant Group × Modality × Stimulus Type interaction ( F (1,141) = 5.29, p = 0.023, η p 2 = 0.036): fasted individuals had similar inhibitory capacity for modal and amodal food stimuli but better inhibitory capacity for non-food words compared to images, while there were no inhibitory differences in dependence on either modality or stimulus type in satiated individuals. Thus, we were able to show that inhibitory capacities to modal compared to amodal stimuli depend on participants' current state of fasting. Future studies should focus on how this lowered inhibitory capacity influences food intake, as well as the role of stimulus valence in cognitive processing, to clarify potential implications for dieting and weight loss training.

Hormonal and neuronal inputs to the brain control how much animals eat. The origins of this behavior were unclear, but in this issue of Cell Reports, Giez et al. 1 describe specific neurons inhibiting feeding in evolutionary ancient animals without brain., Competing Interests: Declaration of interests The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Obesity originates from an imbalance between energy intake and expenditure. Changes in energy intake components (satiation, postprandial satiety, emotional eating) and energy expenditure have been linked to obesity and are referred to as obesity phenotypes. We aim to study if these obesity phenotypes have a cumulative effect on body weight and body mass index (BMI)., Subject/methods: This is a cross-sectional study of adult patients with obesity (BMI > 30 kg/m 2 ) who completed the validated tests to measure the obesity phenotypes. A total of 464 were included in this study., Interventions/methods: We defined higher calories to fullness during an ad libitum meal as abnormal satiation, accelerated time to half gastric emptying with scintigraphy as abnormal postprandial satiety, higher anxiety score on the Hospital Anxiety and Depression Scale as hedonic eating behavior, and decreased percentage of measured resting energy expenditure as abnormal energy expenditure. The primary analysis was done on the number of phenotypes ( ≤ 1 and ≥ 2) with body weight and BMI using an independent t-test., Results: Our cohort included 464 patients (mean [SD] age 42.0 [10.9] years, 79% females, weight 111.2 [22.9] kg, BMI 38.9 [7.0] kg/m 2 ). There were 294 patients who had ≤ 1 phenotype, and 170 patients with ≥ 2 phenotypes with no baseline demographical differences (i.e., age and sex). Having ≥ 2 phenotypes was associated with higher body weight (115 [25] kg vs. 109 [21] kg; p = 0.004), BMI (40 [8] kg/m 2 vs. 38 [7] kg/m 2 ; p = 0.02) and waist (118 [15] cm vs. 115 [13] cm; p = 0.04) and hip (129 [14] cm vs. 125 [13] cm; p = 0.01) circumferences compared to ≤ 1 phenotype., Conclusion: Obesity phenotypes are associated with an additive effect on the body weight and BMI. Patients who have multiple obesity phenotypes may require a more aggressive approach to enhance weight loss., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety., Methods: We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim., Discussion: This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Harries et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals-sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating., (© 2024. The Author(s).)

Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (Oxtr PBN ) in the dorsolateral subdivision of the lateral parabrachial nucleus (dl LPBN) are key neurons which regulate fluid satiation. In the present study, we investigated brain regions activated by stimulation of Oxtr PBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of Oxtr PBN neurons increased Fos expression (a proxy marker for neuronal activation) in known fluid-regulating brain nuclei, as well as other regions that have unclear links to fluid regulation and which are likely involved in regulating other functions such as arousal and stress relief. In addition, we analysed and compared Fos expression patterns between chemogenetically-activated fluid satiation and physiological-induced fluid satiation. Both models of fluid satiation activated similar brain regions, suggesting that the chemogenetic model of stimulating Oxtr PBN neurons is a relevant model of physiological fluid satiation. A deeper understanding of this neural circuit may lead to novel molecular targets and creation of therapeutic agents to treat fluid-related disorders., Competing Interests: Declaration of Competing Interest None Competing interests The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The objectives of this review are to summarize the role of gastric motor functions in the development of satiation (defined broadly as postprandial fullness) and satiety (reduced appetite or postponing desire to eat after a meal) and their impact on weight change. The specific topics are the methods of measurement of gastric emptying and accommodation and their impact on food intake, satiation, and satiety. A second focus contrasts bariatric surgery to endoscopic gastroplasty that alter gastric emptying and incretin responses in markedly divergent manners., Background: The hormone, GLP-1, retards gastric emptying and increases gastric accommodation through vagally-mediated effects. Indeed, these effects provide the basis for the association of altered gastric emptying in the appetite and weight loss responses to pharmacological interventions particularly by those acting on receptors of incretin agonists such as liraglutide and the dual agonists, tirzepatide and cotadutide, all of which retard gastric emptying. In fact, retardation of gastric emptying and gastrointestinal adverse effects have been shown to contribute in part to the weight loss in response to this class of pharmacological agents., Summary: The motor functions of the stomach are relevant to postprandial fullness and to interventions aimed at weight loss in people with obesity., (© 2023 John Wiley & Sons Ltd.)

Small intestinal satiation pathways involve nutrient-induced stimulation of chemoreceptors leading to release of satiety hormones from intestinal enteroendocrine cells (ECCs). Whether adaptations in these pathways contribute to increased maternal food intake during pregnancy is unknown. To determine the expression of intestinal nutrient-sensors and satiety hormone transcripts and proteins across pregnancy in mice. Female C57BL/6J mice (10-12 weeks old) were randomized to mating and then tissue collection at early- (6.5 d), mid- (12.5 d) or late-pregnancy (17.5 d), or to an unmated age matched control group. Relative transcript expression of intestinal fatty acid, peptide and amino acid and carbohydrate chemoreceptors, as well as gut hormones was determined across pregnancy. The density of G-protein coupled receptor 93 (GPR93), free fatty acid receptor (FFAR) 4, cholecystokinin (CCK) and glucagon-like peptide1 (GLP-1) immunopositive cells was then compared between non-pregnant and late-pregnant mice. Duodenal GPR93 expression was lower in late pregnant than non-pregnant mice (P < 0.05). Ileal FFAR1 expression was higher at mid- than at early- or late-pregnancy. Ileal FFAR2 expression was higher at mid-pregnancy than in early pregnancy. Although FFAR4 expression was consistently lower in late-pregnant than non-pregnant mice (P < 0.001), the density of FFAR4 immunopositive cells was higher in the jejunum of late-pregnant than non-pregnant mice. A subset of protein and fatty acid chemoreceptor transcripts undergo region-specific change during murine pregnancy, which could augment hormone release and contribute to increased food intake. Further investigations are needed to determine the functional relevance of these changes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Imagine a bowl of soup that never emptied, no matter how many spoonfuls you ate-when and how would you know to stop eating? Satiation can play a role in regulating eating behavior, but research suggests visual cues may be just as important. In a seminal study by Wansink et al. (2005), researchers used self-refilling bowls to assess how visual cues of portion size would influence intake. The study found that participants who unknowingly ate from self-refilling bowls ate more soup than did participants eating from normal (not self-refilling) bowls. Despite consuming 73% more soup, however, participants in the self-refilling condition did not believe they had consumed more soup, nor did they perceive themselves as more satiated than did participants eating from normal bowls. Given recent concerns regarding the validity of research from the Wansink lab, we conducted a preregistered direct replication study of Wansink et al. (2005) with a more highly powered sample ( N = 464 vs. 54 in the original study). We found that most results replicated, albeit with half the effect size ( d = 0.45 instead of 0.84), with participants in the self-refilling bowl condition eating significantly more soup than those in the control condition. Like the original study, participants in the self-refilling condition did not believe they had consumed any more soup than participants in the control condition. These results suggest that eating can be strongly controlled by visual cues, which can even override satiation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Previously, an intervention involving volitional slow breathing reduced trait food craving with protective effects on cardiac vagal activity (CVA). Breathing with a low inspiration-to-expiration (i/e) ratio also increases CVA. High CVA was separately associated with low unregulated eating and lesser impulsivity. Hence, the present study assessed breathing with a low i/e for effects on state food craving, hunger and satiety, state impulsivity, and heart rate variability (HRV) in healthy obese persons., Methods: Forty obese persons were randomized to two groups. The intervention group (mean age ± SD, 41.15 ± 12.63, M:F, 10:10) practiced metronome-regulated breathing with low i/e at 12 breaths per minute (expiration 72% of total breath duration) and attained expiration 55.8% of total breath duration, while the active control group (mean age ± SD, 44.45 ± 11.06, M:F, 13:07) sat motionless and directed their gaze and awareness to the stationary metronome without modifying their breath consciously. The HRV was recorded before, during, and after breathing intervention (or control) (standard limb lead I, acquisition at 2,000 Hz, with an LF filter = 0.5 Hz and HF filter = 50 Hz). Time-domain and frequency-domain HRV parameters were obtained with Kubios software. State food craving, and hunger and satiety were recorded before and after the intervention/control., Results: The intervention group decreased total state food craving scores and the sub-domains (i.e., desire to eat, positive reinforcement, lack of control and hunger), increased current satisfaction with food, decreased total state impulsivity (repeated measures ANOVA, p &lt; 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p &lt; 0.05 in all cases) during the intervention compared to the preceding baseline. The intervention group also showed an increase in positive mood and a decrease in aroused and negative mood states., Conclusion: Changes in state food craving and impulsivity could be related to an increase in HRV or to changes in subjective relaxation and positive mood or to both., (© 2024 S. Karger AG, Basel.)

Dietary fibers prevent obesity through reduction of hunger and prolongation of satiety. A number of mechanical and endocrine signals from gastrointestinal tract are stimulated by fibers and their fermentation products, reach regions of brain involved in the regulation of appetite, and ultimately reduce food intake. Gastric distention, delayed gastric emptying, prevention of hypoglycemic, increased amounts of unabsorbed nutrients reaching to the ileum, and stimulation of enteroendocrine cells for secretion of cholecystokinin, glucagon-like peptide-1 (GLP-1), and peptide YY are among mechanisms of fibers in decreasing hunger and prolongation of satiety. Fermentation of fibers produces short-chain fatty acids that also stimulates enteroendocrine cells to secrete GLP-1 and PYY. Randomized controlled trials have shown reductions in energy intake and body weight along with increased satiation and reduced hunger following consumption of fibers. Prospective cohort studies have confirmed these results but the extent of weight loss in some studies has been small. Controversies exist between studies particularly for the effect of fibers on the gastrointestinal hormones, subsequent food intake, and the resultant weight loss. More studies are needed before a clear conclusion can be drawn especially for the effect of fibers on appetite-related hormones and weight loss.

This chapter (part one of a trilogy) summarizes the neurobiological foundations of endogenous opioids in the regulation of energy balance and eating behavior, dysregulation of which translates to maladaptive dietary responses in individuals with obesity and eating disorders, including anorexia, bulimia, and binge eating disorder. Knowledge of these neurobiological foundations is vital to researchers' and clinicians' understanding of pathophysiology as well as the science-based development of multidisciplinary diagnoses and treatments for obesity and eating disorders. We highlight mechanisms of endogenous opioids in both homeostatic and hedonic feeding behavior, review research on the dysregulation of food reward that plays a role in a wide array of obesity and disordered eating, and the clinical implications of neurobiological responses to food for current science-based treatments for obesity and eating disorders., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Food intake is regulated by homeostatic and hedonic systems that interact in a complex neuro-hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN., Material & Methods: During an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo-continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30-min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon-like peptide (GLP-1), and peptide YY (PYY) with every pCASL-MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs)., Results: A total of 53 participants, 7 with AN, 17 with NW (body-mass index [BMI] 18.5-24.9 kg/m 2 ), and 29 with OB (BMI ≥30 kg/m 2 ) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post-prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP-1 and PYY, and no change in CCK., Conclusion: Conditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness., (© 2023 John Wiley & Sons Ltd.)

Reward devaluation adaptively controls reward intake. It remains unclear how cortical circuits causally encode reward devaluation in healthy and depressed states. Here, we show that the neural pathway from the anterior cingulate cortex (ACC) to the basolateral amygdala (BLA) employs a dynamic inhibition code to control reward devaluation and depression. Fiber photometry and imaging of ACC pyramidal neurons reveal reward-induced inhibition, which weakens during satiation and becomes further attenuated in depression mouse models. Ablating or inhibiting these neurons desensitizes reward devaluation, causes reward intake increase and ultimate obesity, and ameliorates depression, whereas activating the cells sensitizes reward devaluation, suppresses reward consumption, and produces depression-like behaviors. Among various ACC neuron subpopulations, the BLA-projecting subset bidirectionally regulates reward devaluation and depression-like behaviors. Our study thus uncovers a corticoamygdalar circuit that encodes reward devaluation via blunted inhibition and suggests that enhancing inhibition within this circuit may offer a therapeutic approach for treating depression., Competing Interests: Declaration of interests M.L. serves on Neuron’s scientific advisory board. M.L., Z.Y., and Z.Q. filed a patent related to this work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Chemogenetic activation of oxytocin receptor-expressing neurons in the parabrachial nucleus (Oxtr PBN neurons) acts as a satiation signal for water. In this research, we investigated the effect of activating Oxtr PBN neurons on satiation for different types of fluids. Chemogenetic activation of Oxtr PBN neurons in male and female transgenic Oxtr Cre mice robustly suppressed the rapid, initial (15-min) intake of several solutions after dehydration: water, sucrose, ethanol and saccharin, but only slightly decreased intake of Ensure®, a highly caloric solution (1 kcal/mL; containing 3.72 g protein, 3.27 g fat, 13.42 g carbohydrates, and 1.01 g dietary fibre per 100 mL). Oxtr PBN neuron activation also suppressed cumulative, longer-term (2-h) intake of lower caloric, less palatable solutions, but not highly caloric, palatable solutions. These results suggest that Oxtr PBN neurons predominantly control initial fluid-satiation responses after rehydration, but not longer-term intake of highly caloric, palatable solutions. The suppression of fluid intake was not because of anxiogenesis, but because Oxtr PBN neuron activation decreased anxiety-like behaviour. To investigate the role of different PBN subdivisions on the intake of different solutions, we examined FOS as a proxy marker of PBN neuron activation. Different PBN subdivisions were activated by different solutions: the dorsolateral PBN similarly by all fluids; the external lateral PBN by caloric but not non-caloric solutions; and the central lateral PBN primarily by highly palatable solutions, suggesting PBN subdivisions regulate different aspects of fluid intake. To explore the possible mechanisms underlying the minimal suppression of Ensure® after Oxtr PBN neuron activation, we demonstrated in in vitro slice recordings that the feeding-associated agouti-related peptide (AgRP) inhibited Oxtr PBN neuron firing in a concentration-related manner, suggesting possible inhibition by feeding-related neurocircuitry of fluid satiation neurocircuitry. Overall, this research suggests that although palatable beverages like sucrose- and ethanol-containing beverages activate fluid satiation signals encoded by Oxtr PBN neurons, these neurons can be inhibited by hunger-related signals (agouti-related peptide, AgRP), which may explain why these fluids are often consumed in excess of what is required for fluid satiation., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated 1-4 , but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales., (© 2023. The Author(s).)

Objective: Gastrointestinal symptoms, particularly postprandial fullness, are frequently reported in eating disorders. Limited data exist evaluating how these symptoms change in response to outpatient psychological treatment. The current study sought to describe the course of postprandial fullness and early satiation across psychological treatment for adults with bulimia nervosa and related other specified feeding or eating disorders and to test if anxiety moderates treatment response., Methods: Secondary data analysis was conducted on questionnaire data provided by 30 individuals (80% white, M(SD) age  = 31.43(13.44) years; 90% female) throughout treatment and six-month follow-up in a pilot trial comparing mindfulness and acceptance-based treatment with cognitive-behavioral therapy for bulimia nervosa. Participants completed items from the Rome IV Diagnostic Questionnaire for Adult Functional Gastrointestinal Disorders and the State Trait Anxiety Inventory., Results: Postprandial fullness and early satiation both significantly decreased over time (ds = 1.23-1.54; p's < .001). Baseline trait anxiety moderated this outcome, such that greater decreases were observed for those with higher baseline anxiety (p = .02)., Discussion: Results extend prior work in inpatient samples by providing preliminary data that postprandial fullness and early satiation decrease with outpatient psychological treatment for bulimia nervosa. Baseline anxiety moderated this effect for postprandial fullness. Future work should replicate findings in a larger sample and test anxiety as a mechanism underlying postprandial fullness in eating disorders., Public Significance: The current study found that common gastrointestinal symptoms (postprandial fullness and early satiation) decrease over the course of outpatient psychotherapy for adults with full and subthreshold bulimia nervosa. Postprandial fullness decreased more across time for those high in anxiety., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Loss-of-control (LOC) eating involves a subjective feeling that one cannot stop eating or control one's eating. Individuals with LOC eating may exhibit strong appetitive drives and weak inhibitory control, and these two opposing motivations have been related to EEG measurements of frontal asymmetry or lateralized frontal activation. The present study investigated whether frontal asymmetry is related to hedonic hunger, LOC eating severity and frequency, and eating in the absence of hunger (EAH) in the laboratory. Fifty-nine individuals participated in an ostensible taste study after resting-state electroencephalogram (EEG) recordings. After the EEGs, they were provided a meal to eat until fullness, followed by an array of snacks and instructions to eat as much as they would like. The results indicated that several measures of right-frontal asymmetry were related to greater EAH and greater self-reported LOC eating severity. Although right-frontal asymmetry has been theorized to reflect avoidance motivation, recent evidence suggests it may indicate effortful control during approach-avoidance conflicts. Because individuals with LOC eating presumably experience heightened conflict between drives to eat beyond energy needs and to minimize such eating, those experiencing greater LOC may exert greater effort to manage these conflicting motivations. An integration of these neurobiological correlates of LOC eating may help provide a more comprehensive understanding of LOC eating and inform treatments., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Published by Elsevier Ltd.)

Background: Aversive conditioning weakens the gratifying value of a comfort meal. The aim was to determine the effect of a cognitive intervention to reverse aversive conditioning and restore hedonic postprandial response., Methods: This was a randomized, sham-controlled, single-blind, parallel study that was conducted on 12 healthy women ( n = 6 in each group). The reward value of a comfort meal was measured on different days: at initial exposure, after aversive conditioning (administration of the same meal with a masked fat overload on the previous day) and after a cognitive intervention (disclosing the aversive conditioning paradigm in the test group vs. no explanation in the control group). The primary outcome, digestive wellbeing, was determined using graded scales at regular intervals before and after ingestion., Results: At initial exposure, the comfort meal produced a rewarding experience that was impaired using aversive conditioning; upon re-exposure to the original meal, the cognitive intervention increased meal wanting and liking; improved digestive wellbeing and mood; tended to reduce postprandial satiety, bloating/fullness; and abolished discomfort/pain, thereby restoring the hedonic value of the comfort meal. By contrast, sham intervention had no effects, and the postprandial sensations remained like the responses to the offending meal., Conclusion: In this proof-of-concept study, we demonstrate that in healthy women, a mild, short-term acquired aversion to a comfort meal can be reversed using a cognitive intervention., Clinicaltrials: gov ID: NCT05897411.

Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the 13 C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed., Competing Interests: Declaration of competing interest None, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Intuitive eating involves following internal cues of hunger and satiety to guide eating choices as opposed to responding to external signals, strong emotions, or dietary rules. This style of eating has consistently been shown to be related to better physical and psychological health indicators, and more interventions are being designed and studied to promote this eating style. The current study aimed to identify anticipated facilitators and barriers to following this style of eating among a group of college students enrolled in a larger study of intuitive eating., Method: Following a week of tracking their current eating as part of a larger study, college students read a description of intuitive eating. They then answered three open-ended questions about following intuitive eating including facilitators, barriers, and perceived ability to follow long term. Responses were coded using thematic analysis to identify themes across responses., Results: Among 100 participants, 86 % were female, 46 % were Hispanic (41 % non-Hispanic White, 13 % other race/ethnicity), mean age was 24.3 years, and mean body mass index was 26.2. The most commonly anticipated participant-reported facilitators of intuitive eating were being in touch with the body's needs and hunger cues, positive perceptions of intuitive eating, and health considerations. The most commonly anticipated barriers were logistical constraints (e.g., busyness and mealtimes), difficulty with hunger cues and reactions to food, and negative perceptions of intuitive eating. The majority of participants (64 %) would consider following this style of eating long term., Discussion: This study provides information that can be used to improve efforts aimed at promoting intuitive eating to college students, including marketing intuitive eating interventions, and clarifying misunderstandings of its key tenets that might serve as barriers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

From a public health perspective, much of the interest in the relationship between exercise and appetite rests on the implications for energy balance and obesity. Energy balance reflects a dynamic 2-way interaction between energy expenditure (EE) and energy intake (EI). Physical activity and exercise, and appetite are the behavioural components of EE and EI, respectively. Beyond EE, exercise is a powerful and complex physiological stimulus acting on several bodily systems. There are multiple effects of frequent and prolonged exercise on appetite which include inter alia an increase in fasting hunger, an enhancement of post-prandial satiety, a modulation of the hedonic responses to food and improvements in eating behaviour traits. These lead to variable adjustments in EI and in a reduction in the susceptibility to overconsumption. Frequent and prolonged physical activity and exercise behaviour can strengthen and sensitise the appetite control system, whilst physical inactivity and sedentariness (low level of EE) fails to downregulate EI and can permit overconsumption. Not all of the effects of exercise operate uniformly to drive appetite in the same direction. The complexity of the interaction between EE and EI means that the effects of prolonged exercise are characterised by substantial individual heterogeneity. This leads to variable effects on energy balance and body mass., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The prevalence of alcohol consumption and obesity continues to increase. The aim of this literature review was to give an overview of the association between these two health and socioeconomic problems. Ethanol must be considered as an orexigenic molecule, acting on the cerebral regulation of hunger and satiety and on the mesolimbic reward system. Moreover, studies showed that alcohol blocks the fatty acid beta oxidation, promoting the storage of lipids. Observational and experimental studies struggle to find a solid correlation between the two entities, but they have several biases and limitations. Experts agree to consider ethanol ingestion as a potential contributing factor of the higher obesity rates observed in the last decades., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

This study aimed to evaluate the short-term effect of a common bean baked snack (CBBS) and cooked bean consumption on energy intake, satiety, glycemic response, and palatability in subjects with normal weight ( Study 1 ) and overweight ( Study 2 ) and to determine the glycemic index of CBBS ( Study 3 ). For studies 1 and 2, satiety and glycemic response were measured over 45 min after consuming CBBS, cooked beans or white bread preload, and energy intake at an ad libitum test meal was calculated. Energy intake remained similar after consuming the three preloads in both studies. Compared to white bread, CBBS consumption increased fullness by 52% in subjects with normal weight but not in those with overweight. The CBBS calculated glycemic index was considered low (42). Consumption of low glycemic index CBBS increased satiety in adults with a normal weight. Long-term trials assessing the effects on body weight management are necessary.

Purpose: Early satiety has been identified as one of the mechanisms that may explain the beneficial effects of nuts for reducing obesity. This study compared postprandial changes in appetite-regulating hormones and self-reported appetite ratings after consuming almonds (AL, 15% of energy requirement) or an isocaloric carbohydrate-rich snack bar (SB)., Methods: This is a sub-analysis of baseline assessments of a larger parallel-arm randomised controlled trial in overweight and obese (Body Mass Index 27.5-34.9 kg/m 2 ) adults (25-65 years). After an overnight fast, 140 participants consumed a randomly allocated snack (AL [n = 68] or SB [n = 72]). Appetite-regulating hormones and self-reported appetite sensations, measured using visual analogue scales, were assessed immediately before snack food consumption, and at 30, 60, 90 and 120 min following snack consumption. A sub-set of participants (AL, n = 49; SB, n = 48) then consumed a meal challenge buffet ad libitum to assess subsequent energy intake. An additional appetite rating assessment was administered post buffet at 150 min., Results: Postprandial C-peptide area under the curve (AUC) response was 47% smaller with AL compared to SB (p < 0.001). Glucose-dependent insulinotropic polypeptide, glucagon and pancreatic polypeptide AUC responses were larger with AL compared to SB (18%, p = 0.005; 39% p < 0.001; 45% p < 0.001 respectively). Cholecystokinin, ghrelin, glucagon-like peptide-1, leptin and polypeptide YY AUCs were not different between groups. Self-reported appetite ratings and energy intake following the buffet did not differ between groups., Conclusion: More favourable appetite-regulating hormone responses to AL did not translate into better self-reported appetite or reduced short-term energy consumption. Future studies should investigate implications for longer term appetite regulation., Anzctr Reference Number: ACTRN12618001861246 2018., (© 2022. The Author(s).)

While obesity remains a pressing issue, the wider population continues to be exposed to more digital food content than ever before. Much research has demonstrated the priming effect of visual food content, i.e., exposure to food cues increasing appetite and food intake. In contrast, some recent research points out that repeated imagined consumption can facilitate satiate and decrease food intake. Such findings have been suggested as potential remedies to excessive food cue exposure. However, the practically limitless variety of digital food content available today may undermine satiation attempts. The present work aims to replicate and extend prior findings by introducing a within-subjects baseline comparison, disentangling general and (sensory-) specific eating desires, as well as considering the moderating influence of visual and flavour stimulus variety. Three online studies (n = 1149 total) manipulated food colour and flavour variety and reproducibly revealed a non-linear dose-response pattern of imagined eating: 3 repetitions primed, while 30 repetitions satiated. Priming appeared to be specific to the taste of the exposed stimulus, and satiation, contrary to prior literature, appeared to be more general. Neither colour nor flavour variety reliably moderated any of the responses. Therefore, the results suggest that a more pronounced variety may be required to alter imagery-induced satiation., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Transient sexual experiences can have long-lasting effects on behavioral decisions, but the neural coding that accounts for this change is unclear. We found that the ejaculation experience selectively activated estrogen receptor 2 ( Esr2 )-expressing neurons in the bed nucleus of the stria terminalis (BNST)-BNST Esr2 -and led to persistent decreases in firing threshold for days, during which time the mice displayed sexual satiety. Inhibition of hyperexcited BNST Esr2 elicited fast mating recovery in satiated mice of both sexes. In males, such hyperexcitability reduced mating motivation and was partially mediated by larger HCN (hyperpolarization-activated cyclic nucleotide-gated) currents. Thus, BNST Esr2 not only encode a specific mating action but also represent a persistent state of sexual satiety, and alterations in a neuronal ion channel contribute to sexual experience-dependent long-term changes to mating drive.

There has been no validated digital tool for measuring appetite with a visual analog scale (VAS) through a mobile app using participants' smart phones for data collection in virtual settings. To fill the gap, we developed a digital VAS and conducted a digital cross-over clinical trial by comparing appetite responses measured by this digital tool versus paper-based VAS in 102 participants in a free-living environment. Participants consumed either a 230 or 460 kcal breakfast in randomized order in two virtual sessions, and their appetite was measured over the next 4 h using both tools. The results revealed no significant difference in hunger, fullness, satiety, or desire to eat measured by digital and paper VAS. Paper VAS resulted in a higher prospective consumption score than digital VAS; the difference (1.1 out of 100 points) was statistically significant but not practically relevant. Bland and Altman analysis also indicated consistency in the results from the two methods. In conclusion, digital VAS on a smart phone is a validated tool for appetite measurement in the real world; it provides a new way for researchers to leverage participants' mobile devices for appetite data collection in digital trials.

Memory processes may have several roles in appetite regulation. Here we examine one such role, derived from the animal literature, in which satiety cues lead to the inhibition of rewarding food-related memories. We tested this idea over three studies (n's of 58, 67, 50 respectively), by presenting participants with visual or verbal food cues, and asking them to describe what these foods were like to eat. This recollection task was undertaken hungry and sated. The resulting recollections were then coded and contrasted across state. Irrespective of state, participants took the same time to make their recollections, they were of similar length and included the same amount of sensory detail and affective content. However, in all three studies, sated recollections tended to include more reports about how filling a food would be. This increase in reports of food fillingness across state, was significantly correlated with increases in reports of stomach distension across state. While these results are consistent with the operation of memory inhibition, a further possibility is considered, whereby interoceptive satiety cues are integrated into food-related recollections (but not other recollections) to form a memory-inteorception-combination, thereby drawing attention to the consequences of eating when sated., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Satiation is a key component of food intake regulation as it brings an eating episode to an end. The effect of sex on satiation measurement has not been characterized., Objective: To assess the effects of biological variables on satiation., Design: Retrospective cohort study. We included 959 participants (mean age 39 [SD 12] years; 70.7% female, and BMI 33 kg/m 2 [8]) who had measurements of satiation with a nutrient-drink test to assess volume to fullness (VTF) and maximum tolerated volume (MTV), and/or an ad libitum meal test to assess calories consumed to fullness (CTF). We performed univariate and multiple regression analyses to estimate the contribution of sex to VTF, MTV, and CTF, compared to other biological variables, such as age, weight, height, BMI, waist-to-hip circumference (W/H), and lean mass percentage (LM%), that are known to affect these parameters., Results: Females had higher BMI, W/H, and LM%. VTF, MTV, and CTF were lower in females: 704 [323] vs. 783 [328] mL, p = 0.001; 1226 [384] vs. 1419 [410] mL, p < 0.001; and 871 [291] vs. 1086 [326] kcal, p < 0.001; respectively. Sex was a strong and independent predictor of VTF, MTF and CTF: parameter estimate [PE] = -80.8, p = 0.006; PE = -124.2, p = 0.0007; and PE = -110, p = 0.001; respectively., Conclusions: Sex has a strong effect on satiation measured by VTF, MTV, and CTF, even after adjusting for other biological factors known to affect these parameters. Females seem to integrate intra-meal inhibition signals to consume fewer calories unrelated to body size or composition., Clinical Trial Registration: None., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Research has shown that expected satiety is highly associated with portion-size selection and can vary (kcal-for-kcal) significantly between foods. However, research has not adequately investigated whether current appetite influences relative differences in the expected satiety of foods. This is important to explore to better understand how current motivational state influences food choice and portion selection. This study used 'hypothetical' and 'momentary' expected-satiety assessments to understand whether methods requiring a reflection on current motivational state [momentary] versus more hypothetical considerations when assessing expected satiety can influence the interpretation of results. It was hypothesised that current appetite would only influence relative differences in expected satiety between foods for momentary, but not hypothetical, expected satiety assessments. Participants (n = 54) were shown images of twelve foods, once when hungry and once when full. In each case, they selected a portion for each food to 1) match the expected satiety of a fixed-portion 'standard' food [hypothetical], and 2) stave off hunger until their next meal [momentary]. Results showed that the relative between-food comparison of expected satiety was stable for hypothetical (p=.73) but not momentary assessments (p<.001) suggesting that while current motivational state may influence food choice and portion selection in the moment, more generalised comparisons of the satiating abilities of foods (learned over a longer period) remain stable. This is important 1) for methods in future studies, as immediate dietary intake does not appear to influence hypothetical expected satiety, thus dietary control is not necessary before participants undertake these assessments, and 2) as it confirms that difficulties associated with dietary regulation may not be due to inaccurate hypothetical judgements about foods, but instead appear to be influenced by contextual nuances that occur in the moment., Competing Interests: Declaration of competing interest CJM and LJJ are part of the National Institute for Health Research's Leicester Biomedical Research Centre, which is a partnership between University Hospitals of Leicester NHS Trust, Loughborough University, and the University of Leicester. This report is independent research by the National Institute for Health Research. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Cannabidiol (CBD), a CBR2 agonist with limited psychic effects, antagonizes CB1/CB2 receptors. Allelic variation CNR1 (gene for CBR1) rs806378 and FAAH rs324420 were associated with altered gut motility and sensation. This study aimed to compare the pharmacodynamics and clinical effects of a 4-week treatment with pharmaceutical-grade CBD vs placebo and assess the interactions of FAAH and CNR1 gene variants on the effects of CBD in patients with functional dyspepsia (FD)., Methods: We performed a randomized, double-blinded, placebo-controlled (1:1 ratio) study of CBD b.i.d. (20 mg/kg/d according to the US Food and Drug Administration escalation guidance) in FD patients with nondelayed gastric emptying (GE) at baseline. Symptoms were assessed by validated daily symptom diary (0-4 scale for upper abdominal pain, nausea, and bloating), weekly assessment of adequate relief, Leuven Postprandial Distress Scale (8 symptoms, adjectival scores rated 0-4 for severity), and quality of life (Short-Form Nepean Dyspepsia Index [average of 10 dimensions each on a 5-point scale]). After the 4-week treatment, all patients underwent measurements of GE of solids, gastric volumes, and Ensure nutrient satiation test. Statistical analysis compared 2 treatments for all endpoints and the effects of CBD in association with FAAH rs324420 and CNR1 rs806378., Results: CBD and placebo effects on physiological functions and patient response outcomes were not significantly different. There were borderline CBD treatment-by-genotype interactions: rs806378 CNR1 with Leuven Postprandial Distress Scale ( P = 0.06) and GE solids ( P = 0.12)., Discussion: Approved doses of CBD used off-label do not relieve FD with normal baseline GE of solids or alter gastric motor functions and satiation. CBD treatment-by-gene interactions suggest potential benefits for postprandial distress with CNR1 rs806378 T allele., (Copyright © 2022 by The American College of Gastroenterology.)

Satiety is a complex state, influenced by numerous factors that go beyond food ingestion. Satiety influences food habits and behavior, thus affecting human health. This review provides an overview of physiological mechanisms involved in satiety and of methodologies to assess food intake and satiety in both animal models and humans. The following topics are highlighted: differences between satiety and satiation; how the central nervous system regulates food intake and satiety; the impact of different macronutrients on satiety; and how the manipulation of food composition might influence overall satiety. Bringing together knowledge on this myriad of satiety mechanisms and how we can study them is useful to better understand and control obesity and other eating disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV)., Aim: To evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics., Methods: We conducted a randomised, double-blind, placebo-controlled, single-centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T 1/2 ., Results: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV., Conclusion: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis., Clinic Trials Registry: ClinicalTrials.gov #NCT04849559., (© 2022 John Wiley & Sons Ltd.)

Gamma-aminobutyric acid (GABA) is present in the mammalian brain as the main inhibitory neurotransmitter and in foods. It is widely used as a supplement that regulates brain function through stress-reducing and sleep-enhancing effects. However, its underlying mechanisms remain poorly understood, as it is reportedly unable to cross the blood-brain barrier. Here, we explored whether a single peroral administration of GABA affects feeding behavior as an evaluation of brain function and the involvement of vagal afferent nerves. Peroral GABA at 20 and 200 mg/kg immediately before refeeding suppressed short-term food intake without aversive behaviors in mice. However, GABA administration 30 min before refeeding demonstrated no effects. A rise in circulating GABA concentrations by the peroral administration of 200 mg/kg GABA was similar to that by the intraperitoneal injection of 20 mg/kg GABA, which did not alter feeding. The feeding suppression by peroral GABA was blunted by the denervation of vagal afferents. Unexpectedly, peroral GABA alone did not alter vagal afferent activities histologically. The coadministration of a liquid diet and GABA potentiated the postprandial activation of vagal afferents, thereby enhancing postprandial satiation. In conclusion, dietary GABA activates vagal afferents in collaboration with meals or meal-evoked factors and regulates brain function including feeding behavior.

Background/objectives: Disrupted leptin signaling in vagal afferent neurons contributes to hyperphagia and obesity. Thus, we tested the hypothesis that intrinsic negative regulators of leptin signaling, suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) underlie dysfunctional leptin-mediated vagal afferent satiety signaling during obesity., Methods: Experiments were performed on standard chow-fed control mice, high-fat fed (HFF), or low-fat fed (LFF) mice. SOCS3 and PTP1B expression were quantified using western blot and quantitative PCR. Nodose ganglion neuronal excitability and jejunal afferent sensitivity were measured by patch clamp and extracellular afferent recordings, respectively., Results: Increased expression of SOCS3 and PTP1B were observed in the jejunum of HFF mice. Prolonged incubation with leptin attenuated nodose ganglion neuronal excitability, and this effect was reversed by inhibition of SOCS3. Leptin potentiated jejunal afferent nerve responses to CCK in LFF mice but decreased them in HFF mice. Inhibition of SOCS3 restored impaired vagal afferent neuronal excitability and afferent nerve responses to satiety mediators during obesity. Two-pore domain K + channel (K 2P ) conductance and nitric oxide (NO) production that we previously demonstrated were elevated during obesity were decreased by inhibitions of SOCS3 or PTP1B., Conclusions: This study suggests that obesity impairs vagal afferent sensitivity via SOCS3 and PTP1B, likely as a consequence of obesity-induced hyperleptinemia. The mechanisms underlying leptin resistance appear also to cause a more global impairment of satiety-related vagal afferent responsiveness., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Understanding how neurohormonal gut-brain signaling regulates appetite and satiety is vital for the development of therapies for obesity and altered eating behavior. However, reported brain areas associated with appetite or satiety regulators show inconsistency across functional neuroimaging studies. The aim of this study was to systematically assess the convergence of brain regions modulated by appetite and satiety regulators. Twenty-five studies were considered for qualitative synthesis, and 14 independent studies (20-experiments) found eligible for coordinate-based neuroimaging meta-analyses across 212 participants and 123 foci. We employed two different meta-analysis approaches. The results from the systematic review revealed the modulation of insula, amygdala, hippocampus, and orbitofrontal cortex (OFC) with appetite regulators, where satiety regulators were more associated with caudate nucleus, hypothalamus, thalamus, putamen, anterior cingulate cortex in addition to the insula and OFC. The two neuroimaging meta-analyses methods identified the caudate nucleus as a key area associated with satiety regulators. Our results provide quantitative brain activation maps of neurohormonal gut-brain signaling in heathy-weight adults that can be used to define alterations with eating behavior., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mangos are an understudied fruit rich in fiber and polyphenols that have been linked to better metabolic outcomes and promotion of satiety. The purpose of this study was to examine the effect of mango consumption on postprandial glucose, insulin, and satiety responses. Using a randomized crossover study design, 23 overweight and obese men and women consumed 100 kcal snacks of fresh mangos or isocaloric low-fat cookies on two separate occasions. Insulin and satiety hormones were measured at baseline and 45 min post-snack consumption. Glucose was measured at baseline, 30, 60, 90, and 120 min after snack consumption. Satiety questionnaires were completed at baseline and every 20 min for 120 min post-consumption. Both mangos and low-fat cookies increased insulin, with a significantly lower increase for mangos compared with low-fat cookies at 45 min post-snack consumption ( P  ≤ .05). Glucose increased at 30 min for both snacks; however, the increase was significantly higher for low-fat cookie consumption ( P  ≤ .05). Cholecystokinin increased after mangos and low-fat cookie consumption ( P  ≤ .05); however, no differences were detected between the snacks. Adiponectin increased after mango consumption ( P  ≤ .05) but not after low-fat cookies. Mango consumption reduced hunger, anticipated food consumption and thirst, and increased feelings of fullness ( P  ≤ .05). Low-fat cookie consumption increased fullness for a shorter time period and did not reduce participants' desire to eat. These results suggest that relative to a refined cookie snack, mangos promote greater satiety and improve postprandial glycemic responses. Future research on long-term effects of mango consumption on food intake, weight control, and glucose homeostasis is warranted. Clinical Trial Registration number: #NCT03957928.

Peripheral glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are secreted from enteroendocrine cells, and their plasma concentrations increase in response to eating. While the satiating effect of gut-derived CCK on food-intake control is well documented, the effect of peripheral GLP-1 is less clear. There is evidence that native GLP-1 can inhibit food intake only in the fed state but not in the fasting state. We therefore hypothesized that other gut peptides released during a meal might influence the subsequent effect of endogenous GLP-1 and investigated whether CCK could do so. We found that intraperitoneal injection of CCK in food-restricted mice inhibited food intake during the first 30-minute segment of a 1-hour session of ad libitum chow intake and that mice compensated by increasing their intake during the second half of the session. Importantly, this compensatory behaviour was abolished by an intraperitoneal injection of GLP-1 administered following an intraperitoneal injection of CCK and prior to the 1-hour session. In vivo activation of the free fatty acid 1 (FFA1) receptor with orally administered TAK875 increased plasma CCK concentration and, consistent with the effect of exogenous CCK, we found that prior oral administration of TAK875 increased the eating inhibitory effect of peripherally administered GLP-1. To examine the role of the vagus nerve in this effect, we utilized a saporin-based lesioning procedure to selectively ablate the CCK receptor-expressing gastrointestinal vagal afferent neurones (VANs). We found that the combined anorectic effect of TAK875 and GLP-1 was significantly attenuated in the absence of CCK receptor expressing VANs. Taken together, our results indicate that endogenous CCK interacts with GLP-1 to promote satiation and that activation of the FFA1 receptor can initiate this interaction by stimulating the release of CCK., (© 2021 John Wiley & Sons Ltd.)

Food intake and energy expenditure are key regulators of body weight. To regulate food intake, the brain must integrate physiological signals and hedonic cues. The brain plays an essential role in modulating the appropriate responses to the continuous update of the body energy-status by the peripheral signals and the neuronal pathways that generate the gut-brain axis. This regulation encompasses various steps involved in food consumption, include satiation, satiety, and hunger. It is important to have a comprehensive understanding of the mechanisms that regulate food consumption as well as to standardize the vocabulary for the steps involved. This review discusses the current knowledge of the regulation and the contribution peripheral and central signals at each step of the cycle to control appetite. We also highlight how food intake has been measured. The increasingly complex understanding of regulation and action mechanisms intervening in the gut-brain axis offers ambitious targets for new strategies to control appetite., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Ingested food and water stimulate sensory systems in the oropharyngeal and gastrointestinal areas before absorption 1,2 . These sensory signals modulate brain appetite circuits in a feed-forward manner 3-5 . Emerging evidence suggests that osmolality sensing in the gut rapidly inhibits thirst neurons upon water intake. Nevertheless, it remains unclear how peripheral sensory neurons detect visceral osmolality changes, and how they modulate thirst. Here we use optical and electrical recording combined with genetic approaches to visualize osmolality responses from sensory ganglion neurons. Gut hypotonic stimuli activate a dedicated vagal population distinct from mechanical-, hypertonic- or nutrient-sensitive neurons. We demonstrate that hypotonic responses are mediated by vagal afferents innervating the hepatic portal area (HPA), through which most water and nutrients are absorbed. Eliminating sensory inputs from this area selectively abolished hypotonic but not mechanical responses in vagal neurons. Recording from forebrain thirst neurons and behavioural analyses show that HPA-derived osmolality signals are required for feed-forward thirst satiation and drinking termination. Notably, HPA-innervating vagal afferents do not sense osmolality itself. Instead, these responses are mediated partly by vasoactive intestinal peptide secreted after water ingestion. Together, our results reveal visceral hypoosmolality as an important vagal sensory modality, and that intestinal osmolality change is translated into hormonal signals to regulate thirst circuit activity through the HPA pathway., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The ' time-of-day' modifies the metabolic response to meals, but less data exist on the diurnal variations in the hedonic drive to eat. In the present paper, we evaluate the effects of meal timing and macronutrient composition on metabolic responses and the homeostatic vs. hedonic regulation of appetite. In study 1, 84 young, healthy adults completed an online computer-based task assessing the homeostatic and hedonic drive to eat in the morning and evening. In study 2, 24 healthy, young men received 2 identical (850 kcal each) meals in the morning (8:45 h) and evening (18:00 h), of 2 experimental conditions: (i) regular carbohydrate (CH) meals (regular-CH), and (ii) high carbohydrate (high-CH) meals, containing 50 and 80% of energy from CHs, respectively. Serial blood samples were obtained, and the postprandial feelings of hunger, satiety, wanting and liking were assessed. Study 1 revealed a higher hedonic drive to eat in the evening compared to the morning. Study 2 confirmed this diurnal pattern of hedonic appetite regulation and, moreover, showed increased glucose and insulin responses to the evening meal. Postprandial ghrelin and leptin as well as feelings of hunger and satiety were not different between the mealtimes nor between the macronutrient conditions. In line with this, the homeostatic drive to eat was neither affected by the mealtime nor macronutrient composition. Increased the hedonic drive to eat in the evening may represent a vulnerability to palatable food and, thus, energy overconsumption. Together with lower evening glucose tolerance, these findings reflect an adverse metabolic constellation at the end of the day, especially after the ingestion of CH-rich foods.