Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger.

The function of central appetite neurons is instructing animals to ingest specific nutrient factors that the body needs. Emerging evidence suggests that individual appetite circuits for major nutrients-water, sodium, and food-operate on unique driving and quenching mechanisms. This review focuses on two aspects of appetite regulation. First, we describe the temporal relationship between appetite neuron activity and consumption behaviors. Second, we summarize ingestion-related satiation signals that differentially quench individual appetite circuits. We further discuss how distinct appetite and satiation systems for each factor may contribute to nutrient homeostasis from the functional and evolutional perspectives.

Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption.

Hunger and thirst have distinct goals but control similar ingestive behaviors, and little is known about neural processes that are shared between these behavioral states. We identify glutamatergic neurons in the peri-locus coeruleus (periLCVGLUT2 neurons) as a polysynaptic convergence node from separate energy-sensitive and hydration-sensitive cell populations. We develop methods for stable hindbrain calcium imaging in free-moving mice, which show that periLCVGLUT2 neurons are tuned to ingestive behaviors and respond similarly to food or water consumption. PeriLCVGLUT2 neurons are scalably inhibited by palatability and homeostatic need during consumption. Inhibition of periLCVGLUT2 neurons is rewarding and increases consumption by enhancing palatability and prolonging ingestion duration. These properties comprise a double-negative feedback relationship that sustains food or water consumption without affecting food- or water-seeking. PeriLCVGLUT2 neurons are a hub between hunger and thirst that specifically controls motivation for food and water ingestion, which is a factor that contributes to hedonic overeating and obesity.

Neural landscape diffusion resolves conflicts between needs across time.

Animals perform flexible goal-directed behaviours to satisfy their basic physiological needs1-12. However, little is known about how unitary behaviours are chosen under conflicting needs. Here we reveal principles by which the brain resolves such conflicts between needs across time. We developed an experimental paradigm in which a hungry and thirsty mouse is given free choices between equidistant food and water. We found that mice collect need-appropriate rewards by structuring their choices into persistent bouts with stochastic transitions. High-density electrophysiological recordings during this behaviour revealed distributed single neuron and neuronal population correlates of a persistent internal goal state guiding future choices of the mouse. We captured these phenomena with a mathematical model describing a global need state that noisily diffuses across a shifting energy landscape. Model simulations successfully predicted behavioural and neural data, including population neural dynamics before choice transitions and in response to optogenetic thirst stimulation. These results provide a general framework for resolving conflicts between needs across time, rooted in the emergent properties of need-dependent state persistence and noise-driven shifts between behavioural goals.

Food cue regulation of AGRP hunger neurons guides learning.

Agouti-related peptide (AGRP)-expressing neurons are activated by fasting-this causes hunger1-4, an aversive state that motivates the seeking and consumption of food5,6. Eating returns AGRP neuron activity towards baseline on three distinct timescales: rapidly and transiently following sensory detection of food cues6-8, slowly and longer-lasting in response to nutrients in the gut9,10, and even more slowly and permanently with restoration of energy balance9,11. The rapid regulation by food cues is of particular interest as its neurobiological basis and purpose are unknown. Given that AGRP neuron activity is aversive6, the sensory cue-linked reductions in activity could function to guide behaviour. To evaluate this, we first identified the circuit mediating sensory cue inhibition and then selectively perturbed it to determine function. Here, we show that a lateral hypothalamic glutamatergic â†’ dorsomedial hypothalamic GABAergic (γ-aminobutyric acid-producing)12 → AGRP neuron circuit mediates this regulation. Interference with this circuit impairs food cue inhibition of AGRP neurons and, notably, greatly impairs learning of a sensory cue-initiated food-acquisition task. This is specific for food, as learning of an identical water-acquisition task is unaffected. We propose that decreases in aversive AGRP neuron activity6 mediated by this food-specific circuit increases the incentive salience13 of food cues, and thus facilitates the learning of food-acquisition tasks.

Hunger enhances food-odour attraction through a neuropeptide Y spotlight.

Internal state controls olfaction through poorly understood mechanisms. Odours that represent food, mates, competitors and predators activate parallel neural circuits that may be flexibly shaped by physiological need to alter behavioural outcome1. Here we identify a neuronal mechanism by which hunger selectively promotes attraction to food odours over other olfactory cues. Optogenetic activation of hypothalamic agouti-related peptide (AGRP) neurons enhances attraction to food odours but not to pheromones, and branch-specific activation and inhibition reveal a key role for projections to the paraventricular thalamus. Mice that lack neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail to prefer food odours over pheromones after fasting, and hunger-dependent food-odour attraction is restored by cell-specific NPY rescue in AGRP neurons. Furthermore, acute NPY injection immediately rescues food-odour preference without additional training, indicating that NPY is required for reading olfactory circuits during behavioural expression rather than writing olfactory circuits during odour learning. Together, these findings show that food-odour-responsive neurons comprise an olfactory subcircuit that listens to hunger state through thalamic NPY release, and more generally, provide mechanistic insights into how internal state regulates behaviour.

Availability of food determines the need for sleep in memory consolidation.

Sleep remains a major mystery of biology, with little understood about its basic function. One of the most commonly proposed functions of sleep is the consolidation of memory1-3. However, as conditions such as starvation require the organism to be awake and active4, the ability to switch to a memory consolidation mechanism that is not contingent on sleep may confer an evolutionary advantage. Here we identify an adaptive circuit-based mechanism that enables Drosophila to form sleep-dependent and sleep-independent memory. Flies fed after appetitive conditioning needed increased sleep for memory consolidation, but flies starved after training did not require sleep to form memories. Memory in fed flies is mediated by the anterior-posterior α'/ß' neurons of the mushroom body, while memory under starvation is mediated by medial α'/ß' neurons. Sleep-dependent and sleep-independent memory rely on distinct dopaminergic neurons and corresponding mushroom body output neurons. However, sleep and memory are coupled such that mushroom body neurons required for sleep-dependent memory also promote sleep. Flies lacking Neuropeptide F display sleep-dependent memory even when starved, suggesting that circuit selection is determined by hunger. This plasticity in memory circuits enables flies to retain essential information in changing environments.

An integrative sensor of body states: how the mushroom body modulates behavior depending on physiological context.

The brain constantly compares past and present experiences to predict the future, thereby enabling instantaneous and future behavioral adjustments. Integration of external information with the animal's current internal needs and behavioral state represents a key challenge of the nervous system. Recent advancements in dissecting the function of the Drosophila mushroom body (MB) at the single-cell level have uncovered its three-layered logic and parallel systems conveying positive and negative values during associative learning. This review explores a lesser-known role of the MB in detecting and integrating body states such as hunger, thirst, and sleep, ultimately modulating motivation and sensory-driven decisions based on the physiological state of the fly. State-dependent signals predominantly affect the activity of modulatory MB input neurons (dopaminergic, serotoninergic, and octopaminergic), but also induce plastic changes directly at the level of the MB intrinsic and output neurons. Thus, the MB emerges as a tightly regulated relay station in the insect brain, orchestrating neuroadaptations due to current internal and behavioral states leading to short- but also long-lasting changes in behavior. While these adaptations are crucial to ensure fitness and survival, recent findings also underscore how circuit motifs in the MB may reflect fundamental design principles that contribute to maladaptive behaviors such as addiction or depression-like symptoms.

Physiological Needs: Sensations and Predictions in the Insular Cortex.

Physiological needs create powerful motivations (e.g., thirst and hunger). Studies in humans and animal models have implicated the insular cortex in the neural regulation of physiological needs and need-driven behavior. We review prominent mechanistic models of how the insular cortex might achieve this regulation and present a conceptual and analytical framework for testing these models in healthy and pathological conditions.

The effects of sleep disruption on metabolism, hunger, and satiety, and the influence of psychosocial stress and exercise: A narrative review.

Sleep deficiency is a ubiquitous phenomenon among Americans. In fact, in the United States, ∼78% of teens and 35% of adults currently get less sleep than recommended for their age-group, and the quality of sleep appears to be getting worse for many. The consequences of sleep disruption manifest in a myriad of ways, including insulin resistance and disrupted nutrient metabolism, dysregulation of hunger and satiety, and potentially increased body weight and adiposity. Consequently, inadequate sleep is related to an increased risk of various cardiometabolic diseases, including obesity, diabetes, and heart disease. Exercise has the potential to be an effective therapeutic to counteract the deleterious effects of sleep disruption listed above, whereas chronic psychosocial stress may causally promote sleep disruption and cardiometabolic risk. Here, we provide a narrative review of the current evidence on the consequences of short sleep duration and poor sleep quality on substrate metabolism, circulating appetite hormones, hunger and satiety, and weight gain. Secondly, we provide a brief overview of chronic psychosocial stress and its impact on sleep and metabolic health. Finally, we summarise the current evidence regarding the ability of exercise to counteract the adverse metabolic health effects of sleep disruption. Throughout the review, we highlight areas where additional interrogation and future exploration are necessary.

Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.

PURPOSE: The liver-expressed antimicrobial peptide 2 (LEAP2) is a newly recognized peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) blunting the effects of ghrelin and displaying ghrelin-independent actions. Since the implications of LEAP2 are beginning to be elucidated, we investigated if plasma LEAP2 concentration varies with feeding status or sex and whether it is associated with glucose metabolism and appetite sensations. METHODS: We performed a single test meal study, in which plasma concentrations of LEAP2, ghrelin, insulin and glucose as well as visual analogue scales for hunger, desire to eat, prospective food consumption, fullness were assessed before and 60 min after breakfast in 44 participants (n = 21 females) with normal weight (NW) or overweight/obesity (OW/OB). RESULTS: Pre-prandial plasma LEAP2 concentration was ~ 1.6-fold higher whereas ghrelin was ~ 2.0-fold lower in individuals with OW/OB (p < 0.001) independently of sex. After adjusting for body mass index (BMI) and sex, pre-prandial plasma LEAP2 concentration displayed a direct relationship with BMI (ß: 0.09; 95%CI: 0.05, 0.13; p < 0.001), fat mass (ß: 0.05; 95%CI: 0.01, 0.09; p = 0.010) and glycemia (ß: 0.24; 95%CI: 0.05, 0.43; p = 0.021), whereas plasma ghrelin concentration displayed an inverse relationship with BMI and fat mass but not with glycemia. Postprandial plasma LEAP2 concentration increased ~ 58% in females with OW/OB (p = 0.045) but not in females with NW or in males. Pre-prandial plasma LEAP2 concentration displayed an inverse relationship with hunger score (ß: - 11.16; 95% CI: - 18.52, - 3.79; p = 0.004), in a BMI-, sex- and ghrelin-independent manner. CONCLUSIONS: LEAP2 emerges as a key hormone implicated in the regulation of metabolism and appetite in humans. TRIAL REGISTRATION: The study was retrospectively registered in clinicaltrials.gov (April 2023). CLINICALTRIALS: gov Identifier: NCT05815641.

Post-exercise energy replacement might lead to reduced subsequent energy intake in women with constitutional thinness: Exploratory results from the NUTRILEAN project.

While people with Constitutional Thinness (CT) declare a deep willingness to gain weight, there appetitive responses to energy balance manipulations remain unclear. The present work compares the effect of an acute exercise combined or not with an energy replacement load, on subsequent energy intake, appetite and food reward, between normal weight and women with CT. Anthropometric measurements, body composition (Dual X-ray absorptiometry-DXA) and aerobic capacity (VO2max) were assessed in 10 normal-weight (Body Mass Index-BMI): 20-25 kg/m2) and 10 C T (BMI<17.5 kg/m2) women (18-30 years). They randomly performed i) a resting session (CON); ii) an exercise session (EX); iii) an exercise session with energy replacement (EX + R). Their subsequent ad libitum intake, appetite feelings and food reward were evaluated (Leeds-Food-Preference-Questionnaire). CT showed a lower weight (p < 0,001), BMI(p < 0,001), Fat-Mass (%) (p = 0,003) and Fat-Free Mass (kg) (p < 0,001). CT showed a lower ad libitum energy intake on EX + R compared with CON (p = 0,008) and a higher Relative Energy Intake (REI) on CON compared with EX (p = 0,007) and EX + R (p < 0,001). A lower was observed during EX and EX + R compared with CON (p = 0,006,p = 0,009 respectively) in CT. No condition nor group effect was found for hunger. NW only showed a higher pre-meal fullness on EX + R compared to CON and EX (p < 0,001). Choice (p = 0,030), Explicit Liking (p = 0,016), Explicit Wanting (p = 0,004) and Implicit Wanting (p = 0,035) for taste were higher on EX + R than CON and EX. The decreased EI observed in CT when the exercise-induced energy expenditure is compensated by the ingestion of an equivalent energy load, might contribute to explain the difficulty to increase their energy balance and then induce weight gain. Further studies are needed to better understand their energy balance regulation to propose adapted weight gain strategies.

Differences in dietary acceptability, restraint, disinhibition, and hunger among African American participants randomized to either a vegan or omnivorous soul food diet.

The Nutritious Eating with Soul study was a 24-month, randomized behavioral nutrition intervention among African American adults. This present study, which is a secondary analysis of the NEW Soul study, examined changes in dietary acceptability, restraint, disinhibition, and hunger. Participants (n = 159; 79% female, 74% with ≥ college degree, mean age 48.4 y) were randomized to either a soul food vegan (n = 77) or soul food omnivorous (n = 82) diet and participated in a two-year behavioral nutrition intervention. Questionnaires assessing dietary acceptability (Food Acceptability Questionnaire; FAQ) and dietary restraint, disinhibition, and hunger (Three-Factor Eating Questionnaire; TFEQ) were completed at baseline, 3, 6, 12, and 24 months. Mixed models were specified with main effects (group and time) and interaction effects (group by time) to estimate mean differences in FAQ and TFEQ scores using intent-to-treat analysis. After adjusting for employment, education, food security status, sex, and age, there were no differences in any of the FAQ items, total FAQ score, dietary restraint, disinhibition, and hunger at any timepoint except for one item of the FAQ at 12 months. Participants in the vegan group reported a greater increase in satisfaction after eating a meal than the omnivorous group (mean difference 0.80 ± 0.32, 95% CI 0.18, 1.42; P = 0.01). This is one of the first studies to examine differences in dietary acceptability, hunger, and other eating factors among African American adults randomized to either a vegan or omnivorous soul food diet. The findings highlight that plant-based eating styles are equally acceptable to omnivorous eating patterns and have similar changes in hunger, restraint, and disinhibition. These results suggest that plant-based eating styles can be an acceptable dietary pattern to recommend for cardiovascular disease prevention and may result in greater post-meal satisfaction.

The effect of hunger state on hypothalamic functional connectivity in response to food cues.

The neural underpinnings of the integration of internal and external cues that reflect nutritional status are poorly understood in humans. The hypothalamus is a key integrative area involved in short- and long-term energy intake regulation. Hence, we examined the effect of hunger state on the hypothalamus network using functional magnetic resonance imaging. In a multicenter study, participants performed a food cue viewing task either fasted or sated on two separate days. We evaluated hypothalamic functional connectivity (FC) using psychophysiological interactions during high versus low caloric food cue viewing in 107 adults (divided into four groups based on age and body mass index [BMI]; age range 24-76 years; BMI range 19.5-41.5 kg/m2 ). In the sated compared to the fasted condition, the hypothalamus showed significantly higher FC with the bilateral caudate, the left insula and parts of the left inferior frontal cortex. Interestingly, we observed a significant interaction between hunger state and BMI group in the dorsolateral prefrontal cortex (DLPFC). Participants with normal weight compared to overweight and obesity showed higher FC between the hypothalamus and DLPFC in the fasted condition. The current study showed that task-based FC of the hypothalamus can be modulated by internal (hunger state) and external cues (i.e., food cues with varying caloric content) with a general enhanced communication in the sated state and obesity-associated differences in hypothalamus to DLPFC communication. This could potentially promote overeating in persons with obesity.

Homeostatic circuits selectively gate food cue responses in insular cortex.

Physiological needs bias perception and attention to relevant sensory cues. This process is 'hijacked' by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how 'cognitive' cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food-cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic 'hunger neurons' (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues.

Daily ovarian hormone exposure and loss of control eating in adolescent girls: A registered report.

OBJECTIVE: The daily biobehavioral factors that precipitate loss of control eating (LOCE) in adolescent girls are not well known. Ovarian hormone levels are key biological factors associated with the etiology of eating disorders in adolescent girls. Yet, models on how daily ovarian hormone exposure predicts LOCE in adolescent girls are underdeveloped. The goal of this study is to examine the daily patterns and mechanisms of ovarian hormone levels on LOCE across the menstrual cycle in adolescent girls and the mediating roles of food-related reward anticipation and response inhibition. Ecological momentary assessment (EMA) paired with daily hormonal sampling will be used to examine (1) daily associations between within-person hormones and LOCE, and (2) the mediating role of within-person food-related reward anticipation and response inhibition. METHODS: Normally cycling adolescent girls who have reached menarche will provide daily saliva samples for hormone analysis and complete EMA for 35 days. During EMA, girls will report LOCE and will complete task-based and self-report measures of food-related response inhibition and reward anticipation. DISCUSSION: This work has implications for the development of new real-world biobehavioral models of LOCE in adolescent girls, which will guide theory improvements and treatment for LOCE. Results will provide preliminary evidence for treatment targets for novel interventions for adolescent girls-for example, a response inhibition intervention. PUBLIC SIGNIFICANCE: Adolescent eating disorders are severe mental health conditions, often marked by loss of control eating. Estrogen and progesterone play a role in the development and persistence of loss of control eating. The current study will examine how daily exposure to estrogen and progesterone predicts loss of control eating in adolescent girls and identify possible daily mechanisms linking estrogen and progesterone exposure and loss of control eating.

Disconnect between sympathetically-induced hunger suppression and consumption among highly restrained eaters following stress.

Despite emphasis on findings suggesting restrained eaters increase food consumption under stress, unrestrained eaters' reduction in intake is more robust. Early proposals asserted unrestrained eaters significantly reduced intake after certain threats due to the hunger-inhibiting effects of autonomic influences, presuming unrestrained eaters are more responsive to these effects and restrained eaters rely less on physiological cues for eating. However, scant empirical evidence has substantiated these claims. This study examined whether a sequence exists whereby stress elicits autonomic activation, autonomic activation impacts hunger, and hunger then impacts eating, with dietary restraint altering the hunger-intake link. It was hypothesized that sympathetic nervous system activation would be greatest when ongoing safety from stress was uncertain, sympathetic activation would be linked to reduced hunger, and lower hunger would be associated with attenuated intake. Restraint, conceptualized via Hagan et al.'s (2017) latent restraint factors, was hypothesized to reduce the association between hunger and intake. Female participants (n = 147) were randomized to a stress + certain safety, stress + uncertain safety, or control condition. Sympathetic nervous system activity was recorded prior to a bogus taste test, which quantified ad libitum consumption of highly-palatable snack foods post-stress. Only the stress + uncertain safety condition exhibited greater sympathetic nervous system activity than the control condition. A significant index of moderated serial mediation emerged for Preoccupation with Dieting and Weight-Focused Restraint in the stress + uncertain safety condition. Though sympathetic activation decreased hunger similarly regardless of dietary restraint, only less restrained individuals significantly decreased intake. More restrained individuals ate more despite experiencing lower hunger. The disconnect between hunger and intake in more restrained eaters suggests that focus on enhancing attunement to hunger may yield greater benefit than enhancing restraint. 281 words.

Disinhibition augments thirst perception from two dehydrating stimuli in men.

Physiological systems controlling water and energy ingestion are coordinated. Whether maladaptive eating behavior and appetite for water are linked is unknown. Thus, we sought to investigate the association between maladaptive eating and both thirst and water drinking behavior with two dehydrating conditions. Twenty-two lean men and 20 men with obesity (mean age 32.3 ± 8.4 years and 30.0 ± 11.1 years, respectively) completed the Three-Factor Eating Questionnaire (TFEQ) and Gormally Binge Eating Scale. On separate days, volunteers were dehydrated by a 2-h hypertonic saline infusion and a 24-h water deprivation, and thirst was measured on a 100-mm visual analogue scale (VAS) during each procedure. After each dehydrating condition, ad libitum water intake was measured. In the saline infusion, higher Disinhibition on the TFEQ was associated with thirst in the lean group (ß = 4.2 mm VAS, p = 0.03) but not in the group with obesity (p = 0.51). In the water-deprivation condition, higher Disinhibition was also associated with thirst in the lean group (ß = 5.6 mm VAS, p = 0.01) with the strength of relationship being 3.5-fold stronger than that observed in the group with obesity (ß = 1.6 mm VAS, p = 0.0003). Hunger, Restraint, and binge-eating scores were not associated with thirst in either dehydrating condition (all p > 0.05). Maladaptive eating behaviors were not associated with ad libitum water intake (all p > 0.05). Disinhibition is associated with higher thirst perception in healthy weight individuals and may be attenuated in obesity. The characteristics of disinhibition which typically includes a heightened readiness to eat, may reflect a more general phenotype that also reflects a readiness to drink.

[What is the relationship between alcohol and obesity?] / Quelle relation entre alcool et obésité ?

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.

Les prévalences de la consommation d'alcool et de l'obésité ne cessent d'augmenter. L'objectif de cette revue de la littérature est de donner un aperçu de l'association entre ces deux problématiques sanitaires et socio-économiques. L'éthanol, agissant sur la régulation cérébrale de la faim et de la satiété ainsi que sur le système mésolimbique de la récompense, est à considérer comme une substance orexigène. En outre, il bloque la bêta-oxydation des lipides, prédisposant à leur stockage. Malgré des évidences scientifiques discordantes, qui sont cependant conditionnées par des biais et limitations, les experts sont d'accord de considérer la consommation de boissons alcoolisées comme un probable facteur contribuant à l'incrémentation du taux d'obésité observé lors des dernières décennies.

New Neuroscience of Homeostasis and Drives for Food, Water, and Salt.

Well-being requires the maintenance of energy stores, water, and sodium within permissive zones. The brain, as ringleader, orchestrates their homeostatic control. It senses disturbances, decides what needs to be done next, and then restores balance by altering physiological processes and ingestive drives (i.e., hunger, thirst, and salt appetite). But how the brain orchestrates this control has been unknown until recently ­ largely because we have lacked the ability to elucidate and then probe the underlying neuronal "wiring diagrams." This has changed with the advent of new, transformative neuroscientific tools. When targeted to specific neurons, these tools make it possible to selectively map a neuron's connections, measure its responses to various homeostatic challenges, and experimentally manipulate its activity. This review examines these approaches and then highlights how they are advancing, and in some cases profoundly changing, our understanding of energy, water, and salt homeostasis and the linked ingestive drives.