Central Regulation Of Food Intake Research Articles

The effect of spexin injection and its interaction with nitric oxide, serotonin, and corticotropin receptors on the central regulation of food intake in broilers

Complex homeostatic control mechanisms are tools to adjust the food birds eat and their appetite. Birds and mammals differ in several ways considering food intake regulation. Therefore, this study aimed to investigate the special effects of the intracerebroventricular (ICV) injection of spexin and its interaction with nitric oxide, serotonin and corticotropin receptors on central food intake regulation in broilers. In the test 1, Broilers received ICV injection of saline, PCPA (p-chlorophenylalanine,1.25 µg), spexin (10 nmol) and PCPA+spexin. In test 2–7, 8-OH-DPAT, SB-242084 (5-HT2C, 1.5 µg), L-arginine (Precursor of nitric oxide, 200 nmol), L-NAME (nitric oxide synthetize inhibitor, 100 nmol), Astressin-B (30 µg) and Astressin2-B (30 µg) were injected to Broilers instead of the PCPA. Then, the amount of food received was measured up to 2 h after the injection. The food consumption was significantly decreased by Spexin (10 nmol) (P<0.05). Concomitant injection of SB-242084+spexin attenuated spexin-induced hypophagia (P<0.05). Co-injection of L-arginine+spexin enhanced spexin-induced hypophagia and this effect was reversed by L-NAME (P<0.05). Also, concomitant injection of Astressin-B + spexin or Astressin2-B + spexin enhanced spexin-induced hypophagia (P<0.05). Founded on these observations, spexin-induced hypophagia may be mediated by nitric oxide and 5-HT2C, CRF1, and CRF2 receptors in neonatal broilers.

Peripheral administration of lipidized NPAF and NPFF analogs does not influence central food intake regulation but induces anxiety-like behavior

RF-amide peptides influence multiple physiological processes, including the regulation of appetite, stress responses, behavior, and reproductive and endocrine functions. In this study, we examined the roles of neuropeptide FF receptors (NPFFR1 and NPFFR2) by generating several lipidized analogs of neuropeptide AF (NPAF) and 1DMe, a stable analog of neuropeptide FF (NPFF). These analogs were administered peripherally for the first time to investigate their effects on food intake and other potential physiological outcomes. Lipidized NPAF and 1DMe analogs exhibited enhanced stability and increased pharmacokinetics. These analogs demonstrated preserved high affinity for NPFFR2 in the nanomolar range, while the binding affinity for NPFFR1 was tens of nanomoles. They activated the ERK and Akt signaling pathways in cells overexpressing the NPFFR1 and NPFFR2 receptors.Acute food intake in fasted mice decreased after the peripheral administration of oct-NPAF or oct-1DMe. However, this effect was not as pronounced as that observed after the injection of palm11-PrRP31, a potent anorexigenic compound used as a comparator that binds to GPR10 and the NPFFR2 receptor with high affinity. Neither oct-1DMe nor oct-NPAF decreased food intake or body weight in mice with diet-induced obesity during long-term treatment. In mice treated with oct-1DMe, we observed decreased activity in the central zone during the open field test and decreased activity in the open arms of the elevated plus maze. Furthermore, we observed a decrease in plasma noradrenaline levels and an increase in plasma corticosterone levels, as well as an increase in Crh expression in the hypothalamus. Moreover, neuronal activity in the hypothalamus was increased after treatment with oct-1DMe.In this study, we report that oct-1DMe did not have any long-term effects on the central regulation of food intake; however, it caused anxiety-like behavior.

Peripheral administration of neuropeptide W inhibits gastric emptying in rats: The role of small diameter afferent fibers and cholecystokinin receptors

Neuropeptide W (NPW), a novel hypothalamic peptide, contributes to the central regulation of food intake and energy balance, and suppresses feeding behavior when administered centrally. The aim of our study was to investigate the role of peripherally administered NPW in the modulation of gastric emptying, and to evaluate the participation of afferent fibers, cholecystokinin (CCK) receptors and gastric smooth muscle contractility in the regulatory effects of NPW on gastric motility. In Sprague-Dawley male rats equipped with gastric fistula, gastric emptying rate of the saline and peptone solutions was measured following subcutaneous administration of NPW (0.1 or 5 μg/kg) preceded by subcutaneous injections of saline, CCK-1 or CCK-2 receptor antagonists. Another group of rats with cannulas were injected subcutaneously with capsaicin for afferent denervation before commencing emptying trials. The effect of NPW on carbachol-induced gastric contractility and the role of CCK receptors in gastric smooth muscle contractility were also assessed in gastric strips. Peripheral injection of NPW delayed gastric emptying rate of both caloric and non-caloric liquid test meals, while administration of CCK-1 or CCK-2 receptor antagonists or denervation of small diameter afferents reversed NPW–induced delay in gastric emptying. Moreover, NPW inhibited antrum contractility in the organ bath. Our results revealed that peripherally administered NPW delayed liquid emptying from the stomach via the involvement of small diameter afferent neurons and CCK receptors, and thereby this regulatory role may contribute to its central regulatory role in controlling food intake and energy balance.

The Relationship Between the Blood-Brain-Barrier and the Central Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors.

Diabetes and obesity are growing problems worldwide and are associated with a range of acute and chronic complications, including acute myocardial infarction (AMI) and stroke. Novel anti-diabetic medications designed to treat T2DM, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is), exert beneficial effects on metabolism and the cardiovascular system. However, the underlying mechanisms are poorly understood. GLP-1RAs induce anorexic effects by inhibiting the central regulation of food intake to reduce body weight. Central/peripheral administration of GLP-1RAs inhibits food intake, accompanied by an increase in c-Fos expression in neurons within the paraventricular nucleus (PVN), amygdala, the nucleus of the solitary tract (NTS), area postrema (AP), lateral parabrachial nucleus (LPB) and arcuate nucleus (ARC), induced by the activation of GLP-1 receptors in the central nervous system (CNS). Therefore, GLP-1RAs need to pass through the blood-brain barrier to exert their pharmacological effects. In addition, studies revealed that SGLT-2is could reduce the risk of chronic heart failure in people with type 2 diabetes. SGLT-2 is extensively expressed throughout the CNS, and c-Fos expression was also observed within 2 hours of administration of SGLT-2is in mice. Recent clinical studies reported that SGLT-2is improved hypertension and atrial fibrillation by modulating the “overstimulated” renin-angiotensin-aldosterone system (RAAS) and suppressing the sympathetic nervous system (SNS) by directly/indirectly acting on the rostral ventrolateral medulla. Despite extensive research into the central mechanism of GLP-1RAs and SGLT-2is, the penetration of the blood-brain barrier (BBB) remains controversial. This review discusses the interaction between GLP-1RAs and SGLT-2is and the BBB to induce pharmacological effects via the CNS.

Developmental programming of hypothalamic melanocortin circuits.

The melanocortin system plays a critical role in the central regulation of food intake and energy balance. This system consists of neurons producing pro-opiomelanocortin (POMC), melanocortin receptors (MC4Rs), and the endogenous antagonist agouti-related peptide (AgRP). Pomc and Mc4r deficiency in rodents and humans causes early onset of obesity, whereas a loss of Agrp function is associated with leanness. Accumulating evidence shows that many chronic diseases, including obesity, might originate during early life. The melanocortin system develops during a relatively long period beginning during embryonic life with the birth of POMC and AgRP neurons and continuing postnatally with the assembly of their neuronal circuitry. The development of the melanocortin system requires the tight temporal regulation of molecular factors, such as transcription factors and axon guidance molecules, and cellular mechanisms, such as autophagy. It also involves a complex interplay of endocrine and nutritional factors. The disruption of one or more of these developmental factors can lead to abnormal maturation and function of the melanocortin system and has profound metabolic consequences later in life.

Effects of intracerebroventricular injection of spexin and its interaction with NPY, GalR2 and GalR3 receptors on the central food intake regulation and nutritional behavior in broiler chickens

Food intake and appetite in birds can be adjusted by the complex homeostatic control mechanisms. There seem to be many similarities between mammalian and avian species in terms of the regulatory feeding systems. Therefore, the aim of this study was to investigate the effects of ICV injection of spexin and its interaction with GalR and NPY receptors on central food intake regulation and nutritional behavior in broiler chickens. In experiment 1, chicken received ICV injection of saline, spexin (2.5 nmol), spexin (5 nmol) and spexin (10 nmol). In experiment 2, birds received ICV injection of saline, B5063 (NPY1 receptor antagonist 1.25 µg), spexin (10 nmol) and B5063 + spexin. In experiments 3–6, SF22 (NPY2 receptor antagonist,1.25 µg), ML0891 (NPY5 receptor antagonist,1.25 µg), M871 (GalR2 receptor antagonist,10 nmol) and SNAP37889 (GalR3 receptor antagonist,10 nmol) were injected in chickens instead of B5063. Then food intake was measured until 120 min after the injection and nutritional behavior was monitored at 30 min after the injection. Based on the data, a dose-dependent hypophagia was observed by the injection of spexin (P < 0.05). Concomitant injection of B5063 + spexin enhanced spexin-induced hypophagia (P < 0.05). Co-injection of SNAP37889 + spexin (10 nmol) attenuated -induced hypophagia (P < 0.05). Spexin (5 and 10 nmol) decreased number of steps, jumps, the exploratory food and pecks at 15 min after the injection (P < 0.05). Spexin (5 and 10 nmol) decreased standing time while siting time and rest time increased at 10 min after injection (P < 0.05). Based on observations, spexin-induced hypophagia could be mediated by NPY1 and GalR3 receptors in neonatal broiler chickens.

The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity.

BackgroundChildhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels.MethodsChildren and adolescents with obesity aged 8–18 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA.ResultsA total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng/ml, p = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (p = 0.03, p = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng/ml, p = 0.7) in our population.ConclusionBDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception.

The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level.

Rôle de la génétique et de l’épigénétique dans l’obésité de l’enfant et de l’adolescent

Obesity is a complex, multifactorial disease due to a dysfunction of the hypothalamic control of weight and food intake. The contribution of genetics is constant, but its impact is variable depending on the situations ranging from rare genetic obesities (around 5% of cases) to more frequently polygenic obesity (or common obesity) (95% of cases). Other factors as pre- and post-natal, societal or psychological determinants always interact closely with these genetic factors explaining the high variability of the phenotype and the complex pathophysiology. A true continuum exists between all these situations through the involvement of more or less rare genetic variants located in genes encoding key proteins in the central regulation of food intake. Rare forms of obesity are characterized by their common phenotype including a very early-onset severe obesity (BMI Z score greater than+3 SD early before the age of 3 years) with resistance to medical treatment, and major eating disorders characterized by difficulties in voluntary control of food intake. Central endocrine abnormalities such as hypogonadotropic hypogonadism or GH deficiency for example, and metabolic abnormalities due to abnormal adipose tissue distribution are also associated with variable degrees (Alström syndrome for example). Neuropsychological abnormalities are also present such as neurodevelopmental disorders (intellectual disability with variable intensity and/or adaptive development disorders which are part of many syndromes such as in Prader-Wili Syndrome; autism spectrum disorders (in SH2B1 or MYT1L deficiency for example), cognitive disorders with difficulties in emotional regulation (eg: Bardet-Biedl Syndrome or specific rare variants located on genes of the melanocortin pathway), behavioral or psychiatric disorders, sleep disorders and major hypothalamic dysfunctions (eg: Prader-Willi Syndrome, Smith Magenis syndrome). This better understanding of the mechanisms has made it possible to better precise the associated phenotypes and, recently, to lead to therapeutic innovations targeting these key genes. This evolution helps to quickly envisage the development of a real personalized medicine in early onset obesity using the combination of drug treatments targeted according to the identified genetic anomaly and/or a multidisciplinary global approach targeting the patient's phenotype or even the bariatric surgery in specific situations.

Central regulation of food intake is not affected by inclusion of defatted Tenebrio molitor larvae meal in diets for European sea bass (Dicentrarchus labrax)

The homeostatic regulation of food intake in fish has been thoroughly studied in the last years with dietary nutrient composition is one of the factors involved. Despite several studies addressed the impact of insect meal-based diets in food intake of fish, there is no knowledge about their impact in mechanisms of food intake regulation. This study aimed to explore underlying mechanisms through evaluation of dietary fishmeal (FM) replacement by defatted (d-) Tenebrio molitor (dTM) larvae meal in European sea bass. Fish (55 ± 2 g) fed a FM-based diet (CTRL) were compared with those fed two experimental diets containing increasing levels of dTM to replace 40 and 80% of FM (TM40 and TM80, respectively). After ten weeks of feeding, fish food intake was calculated; samples of plasma and different brain areas (hypothalamus and telencephalon) were collected at different post-prandial times (2, 6 and 24 h after feeding) to evaluate circulating metabolites and mRNA abundance in hypothalamus and telencephalon of neuropeptides involved in food intake regulation. No differences occurred in food intake and weight gain among diets. Plasma cholesterol levels decreased 24 h after feeding in fish fed TM40; fish fed dTM diets had higher cholesterol levels, 2 and 6 h after feeding, than those fed CTRL diet. Increased non-esterified fatty acids (NEFA) levels occurred in plasma of fish fed TM80, regardless of the sampling time. At central level, no changes occurred in the mRNA abundance of neuropeptide Y (npy), agouti-related protein 2 (agrp2), pro-opio melanocortin a (pomca) or cocaine- and amphetamine-related transcript 2 (cartpt2). The obtained results suggest that dietary FM replacement by dTM up to 80% in European sea bass does not affect food intake or its central homeostatic regulation, supporting the use of dTM as FM replacement in diets for European sea bass.

Role of the G protein-coupled receptors GPR84 and GPR119 in the central regulation of food intake in rainbow trout.

We evaluated the role of the G protein-coupled receptors GPR84 and GPR119 in food intake regulation in fish using rainbow trout (Oncorhynchus mykiss) as a model. In the first experiment, we assessed the effects on food intake of intracerebroventricular treatment with agonists of these receptors. In the second experiment, we assessed the impact of the same treatments on mRNA abundance in the hypothalamus and hindbrain of neuropeptides involved in the metabolic control of food intake (npy, agrp1, pomca1 and cartpt) as well as in changes in parameters related to signalling pathways and transcription factors involved in the integrative response leading to neuropeptide production. Treatment with both agonists elicited an anorectic response in rainbow trout attributable to changes observed in the mRNA abundance of the four neuropeptides. Changes in neuropeptides relate to changes observed in mRNA abundance and phosphorylation status of the transcription factor FOXO1. These changes occurred in parallel with changes in the phosphorylation status of AMPKα and Akt, the mRNA abundance of mTOR as well as signalling pathways related to PLCβ and IP3. These results allow us to suggest that (1) at least part of the capacity of fish brain to sense medium-chain fatty acids such as octanoate depends on the function of GPR84, and (2) the capacity of fish brain to sense N-acylethanolamides or triglyceride-derived molecules occurs through the binding of these ligands to GPR119.

The Role of Ventromedial Hypothalamus Receptors in the Central Regulation of Food Intake

Hypothalamus is the most critical center in the brain for regulation of food intake. Hypothalamus performs this function through special nuclei. The most important of these nuclei is PVN, because in addition to receiving input from special hypothalamic nuclei, it also receives input from other regions of the brain, as well circulation. Inputs received from other areas of the brain via special receptors including: MCR, GABA, IR, LepR, CBR, OXR, HR, NPY, D, CRF, and GHSR. Due to the presence of several receptors on VMH, different neurotransmitters and neuromodulators related to central food intake regulation effect on this nucleus. These neurotransmitters include two categories: orexigenic and anorexigenic. Orexigenic neuropeptides such as: NPY, orexin, endocannabinoids, glutamate, urocortin, and ghrelin. Anorexigenic neuropeptides included: MSH, CRF, leptin, insulin, BDNF, histamine, and dopamine. Then, VMH integrates these inputs from the bind of these neurotransmitters to their receptors, and sends the final feedback to other brain regions. The VMH is the first satiety center in the brain, and it receives various inputs from different regions of the brain and circulation via multiple receptors, as well as integrating these inputs and sending the appropriate output to other areas of the brain, VMH plays an important role in central control of food intake. Therefore, throughout this review article would discuss the function of this nucleus on central regulation of food intake via various neuropeptides and receptors. Legend: ARC: Arcuate nucleus. PVN: Paraventricular nucleus. VMH: Ventromedial hypothalamus. SF1: Serotonergic factor 1. BDNF: Brain-derived neurotropic factor. POMC: pro-opiomelanocortin. AgRP/NPY: Agouti related protein/ Neuropeptide Y. VTA: Ventral tegmental area. CB: Endocannabinoidergic neuron. OX: Orexin neuron. TB: Tuberommillary nucleus. H: Histaminergic neuron. D: Dopaminergic neuron. G: Glutamatergic neuron.: Stimulatory projection.: Inhibitory projection.

Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways

ObjectivePerinatal exposure to maternal obesity results in predisposition of offspring to develop obesity later in life. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of food intake as a cause. We aimed to define how maternal obesity impacts early development of the hypothalamus to program lasting dysfunction in feeding regulatory pathways. MethodsMice offspring of diet-induced obese mothers were compared to the offspring of lean control mothers. We analysed gene expression in the fetal hypothalamus, alongside neurosphere assays to investigate the effects of maternal obesity on neural progenitor cell proliferation in vitro. Western blotting was used to investigate the insulin signalling pathway in the fetal hypothalamus. Characterisation of cell type and neuropeptide profile in adulthood was linked with analyses of feeding behaviour. ResultsThere was a reduction in the expression of proliferative genes in the fetal hypothalamus of offspring exposed to maternal obesity. This reduction in proliferation was maintained in vitro when hypothalamic neural progenitor cells were grown as neurospheres. Hypothalamic fetal gene expression and neurosphere growth correlated with maternal body weight and insulin levels. Foetuses of obese mothers showed hypothalamic insulin resistance, which may be causative of reduced proliferation. Furthermore, maternal obesity activated the Notch signalling pathway in neonatal offspring hypothalamus, resulting in decreased neurogenesis. Adult offspring of obese mothers displayed an altered ratio of anorexigenic and orexigenic signals in the arcuate nucleus, associated with an inability to maintain energy homeostasis when metabolically challenged. ConclusionsThese findings show that maternal obesity alters the molecular signature in the developing hypothalamus, which is associated with disrupted growth and development of hypothalamic precursor cells and defective feeding regulation in adulthood. This is the first report of fetal hypothalamic insulin resistance in an obese pregnancy and suggests a mechanism by which maternal obesity causes permanent changes to hypothalamic structure and function.

NF-κB signaling in tanycytes mediates inflammation-induced anorexia

ObjectivesInfections, cancer, and systemic inflammation elicit anorexia. Despite the medical significance of this phenomenon, the question of how peripheral inflammatory mediators affect the central regulation of food intake is incompletely understood. Therefore, we have investigated the sickness behavior induced by the prototypical inflammatory mediator IL-1β. MethodsIL-1β was injected intravenously. To interfere with IL-1β signaling, we deleted the essential modulator of NF-κB signaling (Nemo) in astrocytes and tanycytes. ResultsSystemic IL-1β increased the activity of the transcription factor NF-κB in tanycytes of the mediobasal hypothalamus (MBH). By activating NF-κB signaling, IL-1β induced the expression of cyclooxygenase-2 (Cox-2) and stimulated the release of the anorexigenic prostaglandin E2 (PGE2) from tanycytes. When we deleted Nemo in astrocytes and tanycytes, the IL-1β-induced anorexia was alleviated whereas the fever response and lethargy response were unchanged. Similar results were obtained after the selective deletion of Nemo exclusively in tanycytes. ConclusionsTanycytes form the brain barrier that mediates the anorexic effect of systemic inflammation in the hypothalamus.

Interaction Between Oxytocin and Opioidergic System on Food Intake Regulation in Neonatal Layer Type Chicken

The aim of the current study was to determine possible interaction of central oxytocin and opioidergic system on food intake regulation in neonatal layer-type chicken. In experiment 1, FD3 chicken ICV injected with control solution, oxytocin (10 µg), β-FNA (µ receptor antagonist, 5 µg) and oxytocin (10 µg) + β-FNA were injected. Experiments 2–6 were similar to experiments 1, except chicken injected with nor-BNI (κ receptor antagonist, 5 µg), NTI (δ receptor antagonist, 5 µg), DAMGO (µ receptor agonist, 62.25 pmol), U-50488H (κ receptor agonist, 10 nmol), DPDPE (δ receptor agonist, 20 pmol) instead of β-FNA. In experiment 7, control solution, DAMGO (125 pmol), d(CH2)5Tyr(Me)-[Orn8]-vasotocin (oxytocin antagonist, 5 µg) and DAMGO + d(CH2)5Tyr(Me)-[Orn8]-vasotocin were ICV injected to FD3 chicken. Experiments 8 and 9 were similar to experiments 7, except chicken injected with U-50488H (30 nmol) and DPDPE (40 pmol) instead of DAMGO. Then, cumulative food intake was recorded at 30, 60 and 120 min after injection. According to the results, ICV injection of the oxytocin (10 µg) significantly decreased food intake compared to control group (P < 0.05). Co-injection of the oxytocin + β-FNA and oxytocin + U-50488H significantly decreased hypophagic effect of the oxytocin (P < 0.05). While, co-injection of the oxytocin + nor-BNI or oxytocin + DAMGO significantly amplified hypophagic effect of the oxytocin in chicken (P < 0.05). In addition, ICV injection of DAMGO (125 pmol) significantly decreased cumulative food intake compared to control group (P < 0.05). However, co-addministration of the DAMGO + (CH2)5Tyr(Me)-[Orn8]-vasotocin significantly decreased hypophagic effect of the DAMGO (P < 0.05) in chicken. These results suggested there are interconnection between oxytocin and opioidergic system on central food intake regulation, which mediates via µ and κ opioidergic receptors in neonatal layer-type chicken.

Role of Paraventricular Nucleus in Regulation of Feeding Behaviour and the Design of Intranuclear Neuronal Pathway Communications

Food consumption and body weight regulations are done in the hypothalamus. Indeed, hypothalamus is the brain’s main area in controlling food intake. Hypothalamus controls food intake via special nuclei such as: ARC, PVN, DMH, VMH and LHA. PVN are second order neurons. This nucleus received multiple inputs from different areas of the brain via specific and non-specific receptors. NPYR and α2-adrenoceptors are orexigenic receptors, but Melanocortin receptors are anorexigenic receptors. PVN integrated inputs from multiple areas, and then transmitted various outputs for central regulation of food intake. To identify neural pathways and the role of neurotransmitters on central control of food intake in PVN, multiple researches have been done via injection of various neurotransmitters on the laboratory animals. Leptin applies its effect on regulation of feeding behaviours through arcuate nucleus-paraventricular nucleus axis and MC4R receptor. Also, Insulin is a hypophagic neurotransmitter, and its hypophagic effect applied in PVN via NPY1 and MC4R receptors. Ghrelin has a biphasic effect on food intake in birds and mammals. In birds, ghrelin inhibits food intake, but in mammals stimulated food intake. In birds, ghrelin via 5HT2A receptor on CRF neurons located on PVN reduced food intake. In mammals via GHSR (ghrelin receptor) and NPY1 receptors increased food intake. Somatostatin acts in the brain as an inhibitory and hyperphagic neurotransmitter. Hyperphagic effect of Somatostatin on PVN exert via SST2, OX1 and NPY1 receptors respectively. Therefore, PVN has an important effect on central regulation of food intake via different neurotransmitters and pathway. The role of PVN in central regulation of food intake. ARC arcuate nucleus, PVN paraventricular nucleus, LHA lateral hypothalamus area, CRF Corticotropin-realising factor, POMC pro-opiomelanocortin, CART Cocaine and amphetamine-regulated transcript, NPY/AgRP neuropeptide Y/agouti-related protein, Y1R NPY1 receptor, GHSR growth hormone secretagogues receptor, LEPR Leptin receptor, INSR Insulin receptor, OX1R orexin receptor, MC4R Melanocortin4 receptor, SST2R Somatostatin2 receptor.

Na+/K+-ATPase is involved in the regulation of food intake in rainbow trout but apparently not through brain glucosensing mechanisms

To assess the hypothesis that Na+/K+-ATPase (NKA) is involved in the central regulation of food intake in fish, we observed in a first experiment with rainbow trout (Oncorhynchus mykiss) that intracerebroventricular (ICV) treatment with ouabain decreased food intake. We hypothesized that this effect relates to modulation of glucosensing mechanisms in brain areas (hypothalamus, hindbrain, and telencephalon) involved in food intake control. Therefore, we evaluated in a second experiment, the effect of ICV administration of ouabain, in the absence or in the presence of glucose, on NKA activity, mRNA abundance of different NKA subunits, parameters related to glucosensing, transcription factors, and appetite-related neuropeptides in brain areas involved in the control of food intake. NKA activity and mRNA abundance of nkaα1a and nkaα1c in brain were inhibited by ouabain treatment and partially by glucose. The anorectic effect of ouabain is opposed to the orexigenic effect reported in mammals. The difference might relate to the activity of glucosensing as well as downstream mechanisms involved in food intake regulation. Ouabain inhibited glucosensing mechanisms, which were activated by glucose in hypothalamus and telencephalon. Transcription factors and neuropeptides displayed responses comparable to those elicited by glucose when ouabain was administered alone, but not when glucose and ouabain were administered simultaneously. Ouabain might therefore affect other processes, besides glucosensing mechanisms, generating changes in membrane potential and/or intracellular pathways finally modulating transcription factors and neuropeptide mRNA abundance leading to modified food intake.

Central Opioidergic and Adrenergic systems Mediates Food Intake via α1, α2 and β2 Receptors in Neonatal Layer-Type Chicken

The aim of the current study was to determine possible interaction of central Opioidergic and Adrenergic systems on food intake regulation in neonatal layer-type chicken. In experiment 1, chicken ICV injected with control solution, DAMGO (µopioid receptors agonist, 125 pmol), parazosin (α1 receptor antagonist, 10 nmol) and DAMGO + parazosin. In experiment 2, control solution, DAMGO (125 pmol), yohimbine (α2 receptor antagonist, 13 nmol) and DAMGO + yohimbine were ICV injected. In experiment 3, FD3 birds ICV injected with control solution, DAMGO (125 pmol), metoprolol (β1 receptor antagonist, 24 nmol) and DAMGO + metoprolol. In experiment 4, FD3 chicks received ICV injection of control solution, DAMGO (125 pmol), ICI 118,551 (β2 receptor antagonist, 5 nmol) and DAMGO + ICI 118,551. Experiments 5–8 were similar to experiments 1–4, except chicken injected with DPDPE (δ opioid receptors agonist, 40 nmol) instead of DAMGO. Experiments 9–12 were similar to experiments 1–4, except chicken injected with U-50488H (κ opioid receptors agonist, 30 nmol) instead of DAMGO. Then, cumulative food intake was recorded at 30, 60 and 120 min after injection. According to the results, ICV injection of the DAMGO significantly decreased food intake while DPDPE and U-50488H significantly increased food intake in neonatal layer type chicken (P < 0.05). Co-injection of the DAMGO + ICI 118,551 decreased DAMGO-induced hypophagia (P < 0.05). Also, co-injection of the DPDPE + parazosin diminished hyperphagic effect of the DPDPE (P < 0.05). In addition, co-injection of the U-50488H + yohimbine diminished U-50488H-induced hyperphagia (P < 0.05). These results suggested there are interconnection between adrenergic and opioidergic systems on central food intake regulation which mediates via α1, α2 and β2 receptors in neonatal layer-type chicken.

The pathogenesis of obesity

Body fat mass increases when energy intake exceeds energy expenditure. In the long term, a positive energy balance will result in obesity. The worldwide prevalence of obesity has increased dramatically, posing a serious threat to human health. Therefore, insight in the pathogenesis of obesity is important to identify novel prevention and treatment strategies. This review describes the physiology of energy expenditure and energy intake in the context of body weight gain in humans. We focus on the components of energy expenditure and the regulation of energy intake. Finally, we describe rare monogenetic causes leading to an impairment in central regulation of food intake and obesity.

Upper airway stimulation in obstructive sleep apnea improves glucose metabolism and reduces hedonic drive for food.

Upper airway stimulation is a new and effective second-line treatment for obstructive sleep apnea, but possible consequences on glucose metabolism and central regulation of food intake are unclear. Twenty patients were prospectively studied before and 12 months after obstructive sleep apnea treatment by upper airway stimulation. Respiratory parameters and daytime sleepiness were assessed to document effectiveness of treatment. Glucose metabolism was assessed by the oral glucose tolerance test, and hedonic versus homeostatic drive to eat was characterized. At 12 months, upper airway stimulation significantly improved measures of obstructive sleep apnea (all p < 0.01). Despite no change in body weight, fasting C-peptide insulin resistance index (p = 0.01) as well as insulin and C-peptide levels at 60 min during the oral glucose tolerance test (p < 0.02) were reduced. Hedonic drive to eat was strongly reduced (p < 0.05), while leptin and ghrelin remained unchanged (p > 0.15). Upper airway stimulation is effective in treatment of obstructive sleep apnea and improves glucose metabolism. Reduced hedonic drive to eat might contribute to these metabolic improvements. These promising findings are in need for long-term controlled evaluation of metabolic sequelae of upper airway stimulation and to mechanistically evaluate the metabolic benefits of upper airway stimulation in patients with obstructive sleep apnea.