A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight.

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin (POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis-acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2.1, and ERα. We found that nPE3 originated in the lineage leading to placental mammals and remained under purifying selection in all mammalian orders, although it was lost in Simiiformes (monkeys, apes, and humans) following a unique segmental deletion event. Interestingly, ablation of nPE3 from the mouse genome led to a drastic reduction (>70%) in hypothalamic Pomc mRNA during development and only moderate (<33%) in adult mice. Comparison between double (nPE1 and nPE2) and triple (nPE1, nPE2, and nPE3) enhancer mutants revealed the relative contribution of nPE3 to hypothalamic Pomc expression and its importance in the control of food intake and adiposity in male and female mice. Altogether, these results demonstrate that nPE3 integrates a tripartite cluster of partially redundant enhancers that originated upon a triple convergent evolutionary process in mammals and that is critical for hypothalamic Pomc expression and body weight homeostasis.

A brainstem-hypothalamus neuronal circuit reduces feeding upon heat exposure.

Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain's parenchyma and ventricular system3-8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.

The effect of humate as a feed additive on feed intake, production, and carcass parameters of Angus steers.

Humate may be a valuable livestock feed additive, with potential effects on nutrient utilisation and animal performance. Thus, the aim of this study was to investigate the effect of K Humate S 100R supplementation on the feed intake, liveweight gain, and carcass parameters of Angus steers. Within individual pens, 40 weaned steers were allocated to four treatment groups (n = 10/potassium humate K Humate S100R, Omnia Specialities Australia) for 100 days. The treatment groups included Group 1, 35 g K Humate S100R/animal/day; Group 2, 70 g K Humate S100R/animal/day; Group 3, 140 g K Humate S100R/animal/day; and Control Group, which were not supplemented with K Humate S100R (0 g K Humate S100R/animal/day). Chemical and mineral composition of the feed ingredients, dry matter intake (DMI), and average daily weight gains were recorded. The steers were slaughtered as a single group at a commercial Australian abattoir. Standard measures for hot standard carcass weight, eye muscle area, fat depth and coverage, marbling, ossification, meat and fat colour, dressing percentage and loin pH values at 24-hour postmortem were recorded. It was found that the steers allocated to Group 2 had higher DMI (P = 0.003) and feed conversion ratio (FCR) (P < 0.001) compared with those allocated to Group 1 and the Control Group. The MSA marbling score was lowest for steers allocated to the Control Group (P < 0.05) and comparable for those allocated to Groups 1, 2, and 3. Together, these results demonstrate that increased levels of K Humate S100R supplementation improved the carcass quality, via an increase in MSA. However, further research is warranted on the potential effects of humates supplementation on intramuscular fat associated qualities of beef.

Lesion of NPY Receptor-expressing Neurons in Perifornical Lateral Hypothalamus Attenuates Glucoprivic Feeding.

Glucoprivic feeding is one of several counterregulatory responses (CRRs) that facilitates restoration of euglycemia following acute glucose deficit (glucoprivation). Our previous work established that glucoprivic feeding requires ventrolateral medullary (VLM) catecholamine (CA) neurons that coexpress neuropeptide Y (NPY). However, the connections by which VLM CA/NPY neurons trigger increased feeding are uncertain. We have previously shown that glucoprivation, induced by an anti-glycolygic agent 2-deoxy-D-glucose (2DG), activates perifornical lateral hypothalamus (PeFLH) neurons and that expression of NPY in the VLM CA/NPY neurons is required for glucoprivic feeding. We therefore hypothesized that glucoprivic feeding and possibly other CRRs require NPY-sensitive PeFLH neurons. To test this, we used the ribosomal toxin conjugate NPY-saporin (NPY-SAP) to selectively lesion NPY receptor-expressing neurons in the PeFLH of male rats. We found that NPY-SAP destroyed a significant number of PeFLH neurons, including those expressing orexin, but not those expressing melanin-concentrating hormone. The PeFLH NPY-SAP lesions attenuated 2DG-induced feeding but did not affect 2DG-induced increase in locomotor activity, sympathoadrenal hyperglycemia, or corticosterone release. The 2DG-induced feeding response was also significantly attenuated in NPY-SAP-treated female rats. Interestingly, PeFLH NPY-SAP lesioned male rats had reduced body weights and decreased dark cycle feeding, but this effect was not seen in female rats. We conclude that a NPY projection to the PeFLH is necessary for glucoprivic feeding, but not locomotor activity, hyperglycemia, or corticosterone release, in both male and female rats.

Hypothalamic control of body fat mass by food intake: The key to understanding why obesity should be treated as a disease.

BACKGROUND: Hypothalamic centres have been recognized to play a central role in body weight regulation for nearly 70 years. AIMS: In this review, we will explore the current undersanding of the role the hypothalamus plays in controlling food intake behaviours. MATERIALS AND METHODS: Review of relevant literature from PubMed searches and review article citations. RESULTS: Beginning with autopsy studies showing destructive hypothalamic lesions in patients manifesting hyperphagia and rapid weight gain, followed by animal lesioning studies pinpointing adjacent hypothalamic sites as the 'satiety' centre and the 'feeding' centre of the brain, the neurocircuitry that governs our body weight is now understood to consist of a complex, interconnected network, including the hypothalamus and extending to cortical sites, reward centres and brainstem. Neurons in these sites receive afferent signals from the gastrointestinal tract and adipose tissue indicating food availability, calorie content, as well as body fat mass. DISCUSSION: Integration of these complex signals leads to modulation of the two prime effector systems that defend a body fat mass set point: food intake and energy expenditure. CONCLUSION: Understanding the hypothalamic control of food intake forms the foundation for understanding and managing obesity as a chronic disease.

Activation of neurons in the insular cortex and lateral hypothalamus during food anticipatory period caused by food restriction in mice.

Mice fed a single meal daily at a fixed time display food anticipatory activity (FAA). It has been reported that the insular cortex (IC) plays an essential role in food anticipation, and lateral hypothalamus (LH) regulates the expression of FAA. However, how these areas contribute to FAA production is still unclear. Thus, we examined the temporal and spatial activation pattern of neurons in the IC and LH during the food anticipation period to determine their role in FAA establishment. We observed an increase of c-Fos-positive neurons in the IC and LH, including orexin neurons of male adult C57BL/6 mice. These neurons were gradually activated from the 1st day to 15th day of restricted feeding. The activation of these brain regions, however, peaked at a distinct point in the food restriction procedure. These results suggest that the IC and LH are differently involved in the neural network for FAA production.

Cannabis Sativa targets mediobasal hypothalamic neurons to stimulate appetite.

The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis.

Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets: A Report from the 23rd Annual Harvard Nutrition Obesity Symposium.

Obesity is increasing at an alarming rate. The effectiveness of currently available strategies for the treatment of obesity (including pharmacologic, surgical, and behavioral interventions) is limited. Understanding the neurobiology of appetite and the important drivers of energy intake (EI) can lead to the development of more effective strategies for the prevention and treatment of obesity. Appetite regulation is complex and is influenced by genetic, social, and environmental factors. It is intricately regulated by a complex interplay of endocrine, gastrointestinal, and neural systems. Hormonal and neural signals generated in response to the energy state of the organism and the quality of food eaten are communicated by paracrine, endocrine, and gastrointestinal signals to the nervous system. The central nervous system integrates homeostatic and hedonic signals to regulate appetite. Although there has been an enormous amount of research over many decades regarding the regulation of EI and body weight, research is only now yielding potentially effective treatment strategies for obesity. The purpose of this article is to summarize the key findings presented in June 2022 at the 23rd annual Harvard Nutrition Obesity Symposium entitled "The Neurobiology of Eating Behavior in Obesity: Mechanisms and Therapeutic Targets." Findings presented at the symposium, sponsored by NIH P30 Nutrition Obesity Research Center at Harvard, enhance our current understanding of appetite biology, including innovative techniques used to assess and systematically manipulate critical hedonic processes, which will shape future research and the development of therapeutics for obesity prevention and treatment.

Imagined eating - An investigation of priming and sensory-specific satiety.

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.

Male mice engaging differently in emotional eating present distinct plasmatic and neurological profiles.

Objective: Stressed individuals tend to turn to calorie-rich food, also known as 'comfort food' for the temporary relief it provides. The emotional eating drive is highly variable among subjects. Using a rodent model, we explored the plasmatic and neurobiological differences between 'high and low emotional eaters' (HEE and LEE).Methods: 40 male mice were exposed for 5 weeks to a protocol of unpredictable chronic mild stress. Every 3 or 4 days, they were submitted to a 1-h restraint stress, immediately followed by a 3-h period during which a choice between chow and chocolate sweet cereals was proposed. The dietary intake was measured by weighing. Plasmatic and neurobiological characteristics were compared in mice displaying high vs low intakes.Results: Out of 40 mice, 8 were considered as HEE because of their high post-stress eating score, and 8 as LEE because of their consistent low intake. LEE displayed higher plasma corticosterone and lower levels of NPY than HEE, but acylated and total ghrelin were similar in both groups. In the brain, the abundance of NPY neurons in the arcuate nucleus of the hypothalamus was similar in both groups, but was higher in the ventral hippocampus and the basal lateral amygdala of LEE. The lateral hypothalamus LEE had also more orexin (OX) positive neurons. Both NPY and OX are orexigenic peptides and mood regulators.Discussion: Emotional eating difference was reflected in plasma and brain structures implicated in emotion and eating regulation. These results concur with the psychological side of food consumption.

Sex differences in activation of extra-hypothalamic forebrain areas during hedonic eating.

Palatable foods can stimulate appetite without hunger, and unconstrained overeating underlies obesity and binge eating disorder. Women are more prone to obesity and binge eating than men but the neural causes of individual differences are unknown. In an animal model of hedonic eating, a prior study found that females were more susceptible than males to eat palatable food when sated and that the neuropeptide orexin/hypocretin (ORX) was crucial in both sexes. The current study examined potential extra-hypothalamic forebrain targets of ORX signaling during hedonic eating. We measured Fos induction in the cortical, thalamic, striatal, and amygdalar areas that receive substantial ORX inputs and contain their receptors in hungry and sated male and female rats during palatable (high-sucrose) food consumption. During the test, hungry rats of both sexes ate substantial amounts, and while sated males ate much less than hungry rats, sated females ate as much as hungry rats. The Fos induction analysis identified sex differences in recruitment of specific areas of the medial prefrontal cortex, paraventricular nucleus of the thalamus (PVT), nucleus accumbens (ACB), and central nucleus of the amygdala (CEA), and similar patterns across sexes in the insular cortex. There was a striking activation of the infralimbic cortex in sated males, who consumed the least amount food and unique correlations between the insular cortex, PVT, and CEA, as well as the prelimbic cortex, ACB, and CEA in sated females but not sated males. The study identified key functional circuits that may drive hedonic eating in a sex-specific manner.

Dietary Gamma-Aminobutyric Acid (GABA) Induces Satiation by Enhancing the Postprandial Activation of Vagal Afferent Nerves.

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.

A biobehavioral circadian model of restrictive eating and binge eating.

Caloric consumption occurs in rhythms, typically during daytime, waking hours, marked by peaks at mealtimes. These rhythms are disrupted in individuals with eating disorders; mealtime peaks are blunted and delayed relative to sleep/waketimes. Individuals with eating disorders also tend to experience an overall phase delay in appetite; they lack hunger earlier in the day and experience atypically high hunger later in the day, the latter of which may culminate in binge-eating episodes. This disruptive appetitive behavior-early in the day restrictive eating and later in the day binge eating-may be partially accounted for by circadian disruptions, which play a role in coordinating appetitive rhythms. Moreover, restrictive eating and binge eating themselves may further disrupt circadian synchronization, as meal timing serves as one of many external signals to the central circadian pacemaker. Here, we introduce the biobehavioral circadian model of restrictive eating and binge eating, which posits a central role for circadian disruption in the development and maintenance of restrictive eating and binge eating, highlighting modifiable pathways unacknowledged in existing explanatory models. Evidence supporting this model would implicate the need for biobehavioral circadian regulation interventions to augment existing eating disorder treatments for individuals experiencing circadian rhythm disruption. PUBLIC SIGNIFICANCE: Existing treatments for eating disorders that involve binge eating and restrictive eating mandate a regular pattern of eating; this is largely responsible for early behavioral change. This intervention may work partly by regulating circadian rhythm and diurnal appetitive disruptions. Supplementing existing treatments with additional elements specifically designed to regulate circadian rhythm and diurnal appetitive rhythms may increase the effectiveness of treatments, which presently do not benefit all who receive them.

Hypothalamic AMPK as a possible target for energy balance-related diseases.

Hypothalamic AMP-activated protein kinase (AMPK) is a canonical regulator of energy balance and metabolism at the whole-body level. This makes this enzyme an attractive target for treating energy balance-related diseases. However, targeting AMPK within the hypothalamus presents a challenge related to the specific cellular biodistribution of the enzyme and the need to use clinically safe methods of administration. Current evidence has shown that targeting based on small extracellular vesicles (sEVs) might offer a realistic approach for regulating hypothalamic AMPK. This would allow modulation of both sides of the energy-balance equation, namely food intake and energy expenditure, and therefore of overall metabolism. Moreover, this strategy could provide treatment options not only for obesity but also for catabolic/wasting diseases such as hyperthyroidism, rheumatoid arthritis, and even cancer cachexia.

Health effects of yogurt consumption during paediatric age: a narrative review.

Yogurt is a fermented milk product characterised by a peculiar nutritional composition with live and viable cultures of bacteria. Few studies have analysed the benefits of yogurt consumption on health outcomes during paediatric age. Recent epidemiological studies evaluating the nutritional impact of yogurt have demonstrated its significant contribution to nutrients intakes among children. Thus, consuming yogurt is a strategy to achieve recommended nutrient intake and healthier dietary choices, with potential impact on obesity and cardiometabolic outcome in children. Yogurt's effects on paediatric infectious diseases, gastrointestinal diseases and atopic-related disorders are ascribed to the specific probiotic strain administered. Interestingly, the benefits of yogurt consumption are most likely due to effects mediated through the gut microbiota and the enhancement of innate and adaptive immune responses. Therefore, supplementing standard yogurt cultures with probiotic strains could be useful to promote health at different paediatric ages, although more evidence is needed regarding the strain-related effects and their interplay within the paediatric immune system.

Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice.

Ingested nutrients are proposed to control mammalian behavior by modulating the activity of hypothalamic orexin/hypocretin neurons (HONs). Previous in vitro studies showed that nutrients ubiquitous in mammalian diets, such as non-essential amino acids (AAs) and glucose, modulate HONs in distinct ways. Glucose inhibits HONs, whereas non-essential (but not essential) AAs activate HONs. The latter effect is of particular interest because its purpose is unknown. Here, we show that ingestion of a dietary-relevant mix of non-essential AAs activates HONs and shifts behavior from eating to exploration. These effects persisted despite ablation of a key neural gut → brain communication pathway, the cholecystokinin-sensitive vagal afferents. The behavioral shift induced by the ingested non-essential AAs was recapitulated by targeted HON optostimulation and abolished in mice lacking HONs. Furthermore, lick microstructure analysis indicated that intragastric non-essential AAs and HON optostimulation each reduce the size, but not the frequency, of consumption bouts, thus implicating food palatability modulation as a mechanism for the eating suppression. Collectively, these results suggest that a key purpose of HON activation by ingested, non-essential AAs is to suppress eating and re-initiate food seeking. We propose and discuss possible evolutionary advantages of this, such as optimizing the limited stomach capacity for ingestion of essential nutrients.

Rumen fermentation and epithelial gene expression responses to diet ingredients designed to differ in ruminally degradable protein and fiber supplies.

Although numerous studies exist relating ruminal volatile fatty acid (VFA) concentrations to diet composition and animal performance, minimal information is available describing how VFA dynamics respond to diets within the context of the whole rumen environment. The objective of this study was to characterize how protein and fiber sources affect dry matter intake, rumen pH, fluid dynamics, fermentation parameters, and epithelial gene expression. Four diet treatments (soybean meal or heat-treated soybean meal and beet pulp or timothy hay) were delivered to 10 wethers. The soybean meals served as crude protein (CP) sources while the beet pulp and timothy hay represented neutral detergent fiber (NDF) sources. Feed intake, rumen pH, fluid pool size, and fluid passage rate were unaffected by treatment. Butyrate synthesis and absorption were greater on the beet pulp treatment whereas synthesis and absorption of other VFA remained unchanged. Both CP and NDF treatment effects were associated with numerous VFA interconversions. Expression levels of rumen epithelial genes were not altered by diet treatment. These results indicate that rumen VFA dynamics are altered by changes in dietary sources of nutrients but that intake, rumen environmental parameters, and the rumen epithelium may be less responsive to such changes.

Neuroendocrine Modulation of Food Intake and Eating Behavior.

BACKGROUND: In the first section of this review, we examined the neuroanatomical and neurochemical data on hunger and satiety centers, glucose receptors, sensorial influences on eating behavior, and regulation of energy requirements. The second section is devoted to orexigenic and anorexigenic hormones. OBJECTIVE: This paper aimed to overview and summarize data regarding the role of neuroendocrine regulation of food intake and eating behavior. METHODS: Appropriate keywords and MeSH terms were identified and searched in MEDLINE/ PubMed. References of original articles and reviews were examined. RESULTS: Hunger and satiety center are located in the lateral (LH) and ventromedial hypothalamus (VMH). Lasting aphagia has been observed following a lesion of LH, while hyperphagia is induced by LH stimulation. On the other hand, increased food intake after VMH lesion and aphagia following VMH stimulation in hungry animals has also been reported. Intracellular glucopenia triggers food intake by reducing neuronal activity at the satiety center level. Moreover, sensory influences are regulated by food palatability as the positive hedonic evaluation of food and energy requirement indicates the average amount of food energy needed to balance energy expenditure. Orexigenic and anorexigenic hormones secreted from the gastrointestinal tract and adipose tissue regulate brain areas involved in eating behavior via gastric afferent vagal nerve, circumventricular organ area postrema, or transporter system. Finally, oxytocin (OT) plays a role in reward-related eating by inhibiting sugar intake and decreasing palatable food intake by suppressing the reward circuitry in the brain. Moreover, the anorectic effect of nesfatin-1 is abolished by an OT antagonist.