The milk study protocol: A longitudinal, prospective cohort study of the relationship between human milk metabolic hormone concentration, maternal body composition, and early growth and satiety development in Samoan infants aged 1-4 months.

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.

Effects of sleep deprivation on food-related Pavlovian-instrumental transfer: a randomized crossover experiment.

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.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Oxytocin-receptor-expressing neurons in the lateral parabrachial nucleus activate widespread brain regions predominantly involved in fluid satiation.

Fluid satiation is an important signal and aspect of body fluid homeostasis. Oxytocin-receptor-expressing neurons (OxtrPBN) 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 OxtrPBN neurons in order to better characterise the fluid satiation neurocircuitry in mice. Chemogenetic activation of OxtrPBN 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 OxtrPBN 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.

Associations between sleep and appetitive traits in higher-income preschoolers: A six-month study.

BACKGROUND: Short sleep is consistently linked with childhood obesity, possibly via disrupting appetite hormones and increasing food responsiveness. Few studies have objectively examined this association in early childhood. OBJECTIVE: To evaluate associations of sleep quantity and quality with child appetitive traits and eating in the absence of hunger (EAH) in a higher-income cohort of 86 preschool-age children (age 4.0 ± 0.8 years; 42% female; 93% non-Hispanic white, Northern New England, US). METHODS: Children's sleep duration and quality were assessed via parent report (Children's Sleep Habits Questionnaire, CSHQ) at baseline and 6-month follow-up and via accelerometry at baseline. Parents also completed the Child Eating Behaviors Questionnaire to assess the child's appetitive traits. EAH, an objective measure of overeating, was observed at baseline during an in-person visit. Associations between sleep measures and appetitive traits were examined with linear mixed-effect or linear regression models, as appropriate, adjusting for child age, sex, and household income. RESULTS: Shorter sleep duration per parent report was associated with less satiety responsiveness (standardized ß = 0.14, 95% CI: 0.01, 0.26; p = 0.03). Further, satiety responsiveness was inversely related to EAH (Pearson's r = -0.35, p = 0.02). No associations were found between accelerometer-measured sleep parameters and appetitive traits, and no sleep measures were related to EAH. CONCLUSIONS: Shorter usual sleep, per the parent report, was cross-sectionally associated with reduced satiety responsiveness in this sample of higher-income preschoolers. Future studies should consider whether socioeconomic status may modify the impact of poor sleep on appetitive traits in early childhood.

Effects of hunger and calorie content on visual awareness of food stimuli.

Calorie content and hunger are two fundamental cues acting upon the processing of visually presented food items. However, whether and to which extent they affect visual awareness is still an open question. Here, high- and low-calorie food images administered to hungry or satiated participants were confronted in a breaking-Continuous Flash Suppression paradigm (Experiment 1), measuring the time required to access to visual awareness, and in a Binocular Rivalry paradigm (Experiment 2), quantifying the dominance time in visual awareness. Experiment 1 showed that high-calorie food accessed faster visual awareness, but mostly in satiated participants. Experiment 2 indicated that high-calorie food dominated longer visual awareness, regardless the degree of hunger. We argued that the unconscious advantage (Experiment 1) would represent a default state of the visual system towards highest-energy nutrients, yet the advantage is lost in hunger so to be tuned towards an increased need for any nutritional category. On the other hand, the conscious advantage of high-calorie food (Experiment 2) would represent a conscious perceptual and attentional bias towards highest energy-dense food useful for the actual detection of these stimuli in the environment.

Evolutionary perspectives on substance and behavioural addictions: Distinct and shared pathways to understanding, prediction and prevention.

Addiction poses significant social, health, and criminal issues. Its moderate heritability and early-life impact, affecting reproductive success, poses an evolutionary paradox: why are humans predisposed to addictive behaviours? This paper reviews biological and psychological mechanisms of substance and behavioural addictions, exploring evolutionary explanations for the origin and function of relevant systems. Ancestrally, addiction-related systems promoted fitness through reward-seeking, and possibly self-medication. Today, psychoactive substances disrupt these systems, leading individuals to neglect essential life goals for immediate satisfaction. Behavioural addictions (e.g. video games, social media) often emulate ancestrally beneficial behaviours, making them appealing yet often irrelevant to contemporary success. Evolutionary insights have implications for how addiction is criminalised and stigmatised, propose novel avenues for interventions, anticipate new sources of addiction from emerging technologies such as AI. The emerging potential of glucagon-like peptide 1 (GLP-1) agonists targeting obesity suggest the satiation system may be a natural counter to overactivation of the reward system.

Neuroscience of eating: Pace and portion control.

Satiety-promoting neurons of the hindbrain have long been known for their role in meal termination. An innovative new study now reveals how different hindbrain cell types mediate appetite on distinct timescales.

Does social-norm messaging influence expected satiety and ideal portion-size selection?

A person's perception of how long a food will stave off hunger (expected satiety) and the ideal amount to consume (ideal portion size) are both influenced by food-to-mealtime norms. Here, we examine whether social norms can modulate this effect, in three experimental studies. In study 1 (n = 235) participants were exposed to a social norm suggesting most people enjoyed consuming pasta for breakfast. There was a main effect of food-to-mealtime congruence for expected satiety and ideal portion size (p < 0.001) - participants selected a smaller portion of pasta for breakfast (vs. lunch) - but there were no other main effects/interactions (p ≥ 0.15). Study 2 (n = 200) followed the same approach as study 1, but sought to examine whether the typical volume of food consumed at breakfast and lunch needed to be controlled. Again, there was a main effect of congruence (the same pattern) (p ≤ 0.02) but no other main effects/interactions (p ≥ 0.73). Study 3 (n = 208) followed the same approach as study 2, but the social-norm message was changed to suggest that most people who eat pasta for breakfast found it effectively reduced their hunger. Again, there was a main effect of congruence (the same pattern) (p < 0.001) but no other main effects/interaction (p ≥ 0.26). These studies provide further evidence for the food-to-mealtime effect, but do not provide any evidence that a single, simple social-norm statement can modulate expected satiety or ideal portion size, or interact with the food-to-mealtime effect.

Developmental trajectory of appetitive traits and their bidirectional relations with body mass index from infancy to early childhood.

Appetitive traits, including food responsiveness, enjoyment of food, satiety responsiveness and slowness in eating, are associated with childhood body mass index. Change in appetitive traits from infancy to childhood and the direction of causality between appetitive traits and body mass index are unclear. The present study examined the developmental trajectory of appetitive traits and their bidirectional relations with body mass index, from infancy to early childhood. Mothers in the Pregnancy Eating Attributes Study and follow-up (n = 162) reported child appetitive traits using the Baby and Child Eating Behaviour Questionnaires at ages 6 months and 3.5 years, respectively. Standardized body mass index (zBMI) was calculated from child anthropometrics. Cross-lagged panel models estimated bidirectional relations between appetitive traits and zBMI. Food responsiveness, satiety responsiveness and slowness in eating increased from infancy to early childhood. In cross-lagged panel models, lower infant satiety responsiveness (B ± SE = -0.45 ± 0.19, p = .02) predicted greater child zBMI. Infant zBMI did not predict child appetitive traits (p-values >.36). From infancy to early childhood, appetitive traits may amplify. Appetitive traits, particularly satiety responsiveness, appear to influence body mass index during this period, suggesting early intervention targeting these traits may reduce childhood obesity.

The role of gastric function in control of food intake (and body weight) in relation to obesity, as well as pharmacological and surgical interventions.

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.

Visual cues and food intake: A preregistered replication of Wansink et al. (2005).

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).

Household chaos, child temperament, and structure-related feeding practices in toddlerhood: A moderation analysis.

Structure-related feeding practices may promote intuitive child eating behaviors and foster responsiveness to internal cues of hunger and satiety. Caregivers' ability to engage in structure-related feeding practices likely depends on a complex ecology of factors, including household- and child-characteristics. This study examined associations between household chaos and structure-related feeding practices, and the moderating effect of child temperament. Data were from 275 caregiver-toddler dyads from central Ohio. Child temperament was reported by caregivers when children were 18 months of age, whereas household chaos and structure-related feeding practices were reported by caregivers when children were 36 months of age. Multivariable linear regression models were constructed to assess the relationship between chaos and structure-related feeding practices. Interaction terms between household chaos and three dimensions of child temperament were tested to determine whether temperament moderated the relationship between chaos and structure-related feeding practices. Household chaos was not independently associated with structure-related feeding practices, but higher levels of child effortful control were associated with greater mealtime structure. There was a statistically significant interaction between household chaos and child temperamental surgency, such that greater levels of chaos were associated with less structured mealtimes, but only when children had low-surgency. Findings suggest household chaos and child temperament inform caregiver feeding practices, but the influence of chaos may depend on more proximal factors, like child temperament. Recommendations to improve caregiver-child feeding interactions should be sensitive to characteristics of the broader family home environment.

Effect of pregnancy on the expression of nutrient-sensors and satiety hormones in mice.

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.

Neurohormonal response patterns to hunger, satiation, and postprandial fullness in normal weight, anorexia nervosa, and obesity.

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/m2 ), and 29 with OB (BMI ≥30 kg/m2 ) 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.

Meat- and plant-based products induced similar satiation which was not affected by multimodal augmentation.

Little is known about how plant-based products influence satiation compared to corresponding meat-based products. As augmented reality (AR) intensifies sensory experiences, it was hypothesized to improve satiation. This study compared satiation between intake of meatballs and plant-based balls and plant-based balls intensified with AR for visual, olfactory, and haptic sensory properties. Intake order of the meatballs, plant-based balls, and augmented plant-based balls, eaten on separate days, was randomized. Satiation was measured from twenty-eight non-obese adults as ad libitum intake of the balls and extra snacks, and as subjective appetite sensations. Liking and wanting to eat the products were also investigated. There were no differences between the products in satiation. Before tasting the augmented plant-based balls were less liked than the meatballs (p = 0.002) or plant-based balls (p = 0.046), but after eating the first ball or eating the ad libitum number of balls the differences in liking disappeared. Wanting evaluations were similar for each product and decreased during eating (p < 0.001). A group of participants susceptible to AR was found (n = 11), described by decreased intake when augmentation was applied. Among the sub-group, wanting to eat the augmented balls was lower before tasting (p = 0.019) and after eating the first ball (p = 0.002) and appetite was less suppressed after eating the balls ad libitum (p = 0.01), when compared to non-susceptible participants. We conclude that meatballs and plant-based balls were equal in inducing satiation, and multisensory augmentation did not influence satiation. However, the augmentation decreased liking evaluations before tasting. Further studies are needed to explore differences between consumer groups in susceptibility to augmentation.

Reversal of Conditioned Food Aversion Using a Cognitive Intervention: A Sham-Controlled, Randomized, Parallel Study.

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.

Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response.

OBJECTIVE: The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. DESIGN: A crossover study involving two study days for each participant. PARTICIPANTS: Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). INTERVENTIONS: Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. PRIMARY OUTCOMES: Difference in appetite and satiety sensations during OGTT and IIGI. RESULTS: Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). CONCLUSIONS: Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. TRIAL REGISTRY NO: ClinicalTrials.gov: NCT01492283 and NCT06064084.

Sequential appetite suppression by oral and visceral feedback to the brainstem.

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 integrated1-4, 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.

Feeding signals inhibit fluid-satiation signals in the mouse lateral parabrachial nucleus to increase intake of highly palatable, caloric solutions.

Chemogenetic activation of oxytocin receptor-expressing neurons in the parabrachial nucleus (OxtrPBN neurons) acts as a satiation signal for water. In this research, we investigated the effect of activating OxtrPBN neurons on satiation for different types of fluids. Chemogenetic activation of OxtrPBN neurons in male and female transgenic OxtrCre 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). OxtrPBN 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 OxtrPBN 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 OxtrPBN 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 OxtrPBN neuron activation, we demonstrated in in vitro slice recordings that the feeding-associated agouti-related peptide (AgRP) inhibited OxtrPBN 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 OxtrPBN 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.