Hunger, Satiety, and Their Vulnerabilities.

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.

Acute exercise might not affect subsequent appetite responses to a fixed meal in adolescents with obesity: The SMASH exploratory study.

While an intensity-dependent post-exercise decrease in energy intake (EI) has been described in adolescents with obesity, studies invariably used ad libitum meals, limiting then any conclusions regarding the effect of exercise on post-meal appetitive responses that can be also impacted by the ad libitum nature of the meal. This study analyses appetite and food-reward related responses to a fixed meal after an acute exercise, also exploring the associations between substrate use during exercise and overall daily EI in adolescents with obesity. Thirteen adolescents with obesity (12-16 years, 5 males) randomly complete 2 experimental sessions: (i) a control condition (CON); (ii) a 30-min moderate intensity (65% VO2peak) cycling condition (EX). Energy expenditure and substrate oxidation were measured during both 30 min of rest (CON) or exercise (EX). Ad libitum EI, macronutrient intake and relative EI were assessed at dinner, subjective appetite sensations taken at regular intervals and food reward measured before and after lunch as well as before dinner. Energy and macronutrient intake did not differ between conditions, as well as appetite feelings. A time effect (p = 0.012) was observed between pre and post meal for choice fat bias in both conditions but was only significant within the CON condition (p = 0.004). CHO oxidation during exercise was found correlated with both EI (r = 0.586, p = 0.045), pre-lunch hunger (r = 0.624, p = 0.030), daily AUC for hunger and DTE (r = 0.788, p = 0.002 and r = 0.695; p = 0.012 respectively). This exploratory study highlights that acute exercise might not affect subsequent appetite responses when using a fixed test meal in adolescents with obesity.

Lunch melodies: Investigating the impact of music on emotions, hunger, liking, and psychophysiology while viewing a lunch meal.

Sensory cues like music can influence our behaviour towards food. In the present study, the effect of music on hunger, fullness, desire to eat and liking of foods, while viewing real lunch food items, was investigated. To this end, emotions and physiological measures were obtained to understand the changes in hunger, fullness, desire to eat and liking. The study aimed to examine changes in hunger, fullness, desire to eat, and liking when viewing a lunch meal under silent and varying music conditions. Additionally, the study explored the potential role of emotions to explain these changes. A crossover experimental design was employed using 50 participants (17 males and 33 females) who observed lunch food items during a silent condition (control), or while listening to either liked or disliked music. The findings demonstrate the cross-modal influence of music on hunger and food liking ratings when viewing food. Hunger ratings were higher and more negative emotions were evoked while viewing lunch food items and listening to disliked music. In contrast, in the silent and liked music conditions, which elicited more positive emotions, there were increased ratings of healthy and unhealthy food pleasantness, overall food liking, and food satisfaction. Electrophysiological measures of heart rate (HR) and skin conductance (SC) were obtained while listening to music and viewing a lunch meal. Viewing food items while listening to disliked music evoked negative emotions and significantly increased SC compared to liked music or silent conditions. Viewing the food items under the silent condition evoked positive emotions and significantly increased HR compared to listening to liked and disliked music. This study showed that the participants' emotions, hunger level, liking, and electrophysiological responses when viewing food are influenced by music that varied with liking. Results from this study may assist in enhancing dining experiences, as well as influencing food choices and satisfaction with meals.

Influence of short-time resistance training on appetite and energy intake in young women with and without obesity.

The aim of this study was to investigate the effect of 6-weeks resistance training (RT) on appetite, energy intake and body composition in young women with and without obesity, and to examine the relationship between these variables. Thirty-five young women were divided according to the amount of body fat [with obesity (n = 16) and without obesity (n = 19)]. Appetite was assessed through self-reported hunger, fullness, desire to eat, satiety quotient, food frequency diary and motivations to eat palatable food (power of food scale) in both fasted and fed states (after a standardized breakfast). Energy intake and body composition were evaluated at pre- and post-6 weeks of RT. Results showed that self-reported hunger increased significantly in both fasted and fed states (p = 0.007 and p = 0.029, respectively), while self-reported fullness decreased at the fasted state (p = 0.030) in both groups. There were no significant effects for desire to eat fatty, sweet, savory and salty foods, motivation to eat palatable foods, or for total energy intake. Food frequency analysis indicated a decrease in consumption of soup and past (p = 0.045), vegetables and eggs (p = 0.034), and leafy vegetables (p = 0.022) in both groups. Fat-free mass increased significantly in both groups (p = 0.011 and p = 0.003), while fat mass did not show significant changes. There were no correlations between changes in appetite/energy intake and changes in body composition. In conclusion, following the 6-week RT program, both women with and without obesity exhibited increased self-reported hunger alongside decreased fullness, suggesting an increase in orexigenic drive. However, neither group showed an increase in energy intake and fat mass, while both groups experienced an increase in fat-free mass. Registered under Brazilian Registry of Clinical Trials n°. RBR-1024f4qs.

A Method for Evaluating Hunger and Thirst in Monkeys by Measuring Blood Ghrelin and Osmolality Levels.

Hunger and thirst drive animals' consumption behavior and regulate their decision-making concerning rewards. We previously assessed the thirst states of monkeys by measuring blood osmolality under controlled water access and examined how these thirst states influenced their risk-taking behavior in decisions involving fluid rewards. However, hunger assessment in monkeys remains poorly performed. Moreover, the lack of precise measures for hunger states leads to another issue regarding how hunger and thirst states interact with each other in each individual. Thus, when controlling food access to motivate performance, it remains unclear how these two physiological needs are satisfied in captive monkeys. Here, we measured blood ghrelin and osmolality levels to respectively assess hunger and thirst in four captive macaques. Using an enzyme-linked immunosorbent assay, we identified that the levels of blood ghrelin, a widely measured hunger-related peptide hormone in humans, were high after 20 h of no food access (with ad libitum water). This reflects a typical controlled food access condition. One hour after consuming a regular dry meal, the blood ghrelin levels in three out of four monkeys decreased to within their baseline range. Additionally, blood osmolality measured from the same blood sample, the standard hematological index of hydration status, increased after consuming the regular dry meal with no water access. Thus, ghrelin and osmolality may reflect the physiological states of individual monkeys regarding hunger and thirst, suggesting that these indices can be used as tools for monitoring hunger and thirst levels that mediate an animal's decision to consume rewards.

Volitionally Regulated Breathing with Prolonged Expiration Influences Food Craving and Impulsivity.

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 < 0.05 in all cases), increased HF-HRV and RMSSD (linear mixed model analyses with age and gender as fixed factors; p < 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.

Caregivers' Attention Toward, and Response to, Their Child's Interoceptive Hunger and Thirst Cues.

People can use their internal state to determine if they are hungry or thirsty. Although the meaning of some interoceptive cues may be innate (e.g., pain), it is possible that others-including those for hunger and thirst-are acquired. There has been little exploration of this idea in humans. Consequently, we conducted a survey among child caregivers to determine if the basic conditions necessary for interoceptive learning were present. Two-hundred and thirty-five caregivers of children aged 1-12 years were asked if they had recently noticed stomach rumbling, hunger-related irritability, and a dry mouth in their child. They were also asked how they would respond. The impact of several moderating variables, especially caregiver beliefs about the causes of hunger, fullness, and thirst, was also explored. Fifteen percent of caregivers had recently noticed stomach rumbling in their child, 28% hunger-related irritability, and 14% a dry mouth. Forty-four percent of caregivers had noticed at least one of these three cues. Noticing hunger cues was significantly moderated by caregiver beliefs about their cause, by child age, and in one case by temporal context (around vs. outside mealtimes). Key caregiver responses were providing the need (e.g., offer food) and/or asking the child if they had a need (e.g., hungry?). Each type of response could potentially support a different form of interoceptive learning. In conclusion, we suggest the necessary conditions for children to learn interoceptive hunger and thirst cues, are present in many caregiver-offspring dyads.

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.

Low-calorie diet-induced weight loss is associated with altered brain connectivity and food desire in obesity.

OBJECTIVE: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity. METHODS: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis. RESULTS: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger. CONCLUSIONS: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.

NPY-mediated synaptic plasticity in the extended amygdala prioritizes feeding during starvation.

Efficient control of feeding behavior requires the coordinated adjustment of complex motivational and affective neurocircuits. Neuropeptides from energy-sensing hypothalamic neurons are potent feeding modulators, but how these endogenous signals shape relevant circuits remains unclear. Here, we examine how the orexigenic neuropeptide Y (NPY) adapts GABAergic inputs to the bed nucleus of the stria terminalis (BNST). We find that fasting increases synaptic connectivity between agouti-related peptide (AgRP)-expressing 'hunger' and BNST neurons, a circuit that promotes feeding. In contrast, GABAergic input from the central amygdala (CeA), an extended amygdala circuit that decreases feeding, is reduced. Activating NPY-expressing AgRP neurons evokes these synaptic adaptations, which are absent in NPY-deficient mice. Moreover, fasting diminishes the ability of CeA projections in the BNST to suppress food intake, and NPY-deficient mice fail to decrease anxiety in order to promote feeding. Thus, AgRP neurons drive input-specific synaptic plasticity, enabling a selective shift in hunger and anxiety signaling during starvation through NPY.

Endogenous Opioids in the Homeostatic Regulation of Hunger, Satiety, and Hedonic Eating: Neurobiological Foundations.

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.

Hunger and satiety: Neuronal dynamics in Hydra behavior.

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.

Compensatory enhancement of input maintains aversive dopaminergic reinforcement in hungry Drosophila.

Hungry animals need compensatory mechanisms to maintain flexible brain function, while modulation reconfigures circuits to prioritize resource seeking. In Drosophila, hunger inhibits aversively reinforcing dopaminergic neurons (DANs) to permit the expression of food-seeking memories. Multitasking the reinforcement system for motivation potentially undermines aversive learning. We find that chronic hunger mildly enhances aversive learning and that satiated-baseline and hunger-enhanced learning require endocrine adipokinetic hormone (AKH) signaling. Circulating AKH influences aversive learning via its receptor in four neurons in the ventral brain, two of which are octopaminergic. Connectomics revealed AKH receptor-expressing neurons to be upstream of several classes of ascending neurons, many of which are presynaptic to aversively reinforcing DANs. Octopaminergic modulation of and output from at least one of these ascending pathways is required for shock- and bitter-taste-reinforced aversive learning. We propose that coordinated enhancement of input compensates for hunger-directed inhibition of aversive DANs to preserve reinforcement when required.

AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin's acute effects.

AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons.

Metabolic sensing in AgRP regulates sucrose preference and dopamine release in the nucleus accumbens.

Hunger increases the motivation for calorie consumption, often at the expense of low-taste appeal. However, the neural mechanisms integrating calorie-sensing with increased motivation for calorie consumption remain unknown. Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus sense hunger, and the ingestion of caloric solutions promotes dopamine release in the absence of sweet taste perception. Therefore, we hypothesised that metabolic-sensing of hunger by AgRP neurons would be essential to promote dopamine release in the nucleus accumbens in response to caloric, but not non-caloric solutions. Moreover, we examined whether metabolic sensing in AgRP neurons affected taste preference for bitter solutions under conditions of energy need. Here we show that impaired metabolic sensing in AgRP neurons attenuated nucleus accumbens dopamine release in response to sucrose, but not saccharin, consumption. Furthermore, metabolic sensing in AgRP neurons was essential to distinguish nucleus accumbens dopamine response to sucrose consumption when compared with saccharin. Under conditions of hunger, metabolic sensing in AgRP neurons increased the preference for sucrose solutions laced with the bitter tastant, quinine, to ensure calorie consumption, whereas mice with impaired metabolic sensing in AgRP neurons maintained a strong aversion to sucrose/quinine solutions despite ongoing hunger. In conclusion, we demonstrate normal metabolic sensing in AgRP neurons drives the preference for calorie consumption, primarily when needed, by engaging dopamine release in the nucleus accumbens.

Comparison of 8-weeks of full versus split body resistance training on appetite and energy intake in non-obese untrained men.

To investigate the effects of 8-weeks of full versus split body resistance training (RT) on appetite and energy intake in non-obese untrained men. The participants were pair-matched based on their initial fat mass and then randomly allocated into one of two treatment groups: Full body (FB, n = 20), in which all muscle groups were trained in every session, or Split body (SB, n = 15), in which upper and lower muscle groups were trained alternated per session; both groups trained in non-consecutive days, three times per week with total number of sets performed equated between groups. Energy intake, body composition, and strength performance were evaluated at pre-training, and after 8-weeks of RT, as well as self-reported hunger, fullness, and desire to eat, that were assessed at fasted and feed states pre- and post-intervention. FB and SB resistance training increased fat-free mass (FFM) (p < 0.001); and FB induced greater maximal strength improvement (p = 0.027). At fasted state self-reported hunger increased, and fullness decreased, while in feed state desire to eat something fatty increased in both groups. Carbohydrate intake (p = 0.011) decreased in both groups. In conclusion, FB and SB training increased orexigenic drive (increasing hunger and decreasing fullness), however, total energy intake and fat mass did not change after 8-weeks of RT in non-obese untrained men.Registered under Brazilian Registry of Clinical Trials no. RBR-3wkcvyw.

microRNA-33 controls hunger signaling in hypothalamic AgRP neurons.

AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.