Stimulate Food Intake Research Articles

Involvement of Astrocytes in Mediating the Central Effects of Ghrelin

Although astrocytes are the most abundant cells in the mammalian brain, much remains to be learned about their molecular and functional features. Astrocytes express receptors for numerous hormones and metabolic factors, including the appetite-promoting hormone ghrelin. The metabolic effects of ghrelin are largely opposite to those of leptin, as it stimulates food intake and decreases energy expenditure. Ghrelin is also involved in glucose-sensing and glucose homeostasis. The widespread expression of the ghrelin receptor in the central nervous system suggests that this hormone is not only involved in metabolism, but also in other essential functions in the brain. In fact, ghrelin has been shown to promote cell survival and neuroprotection, with some studies exploring the use of ghrelin as a therapeutic agent against metabolic and neurodegenerative diseases. In this review, we highlight the possible role of glial cells as mediators of ghrelin’s actions within the brain.

From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation.

Ghrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging. This is due to many factors, ranging from the complexity of the ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR-1a) internalisation and heterodimerization, to biased ligand interactions and compensatory neuroendocrine outputs. Not least is the ubiquitous expression of the GHSR-1a, which makes it impossible to modulate centrally-mediated appetite regulation without encroaching on the various peripheral functions attributable to ghrelin. It is becoming clear that ghrelin’s central signalling is critical for its effects on appetite, body weight regulation and incentive salience of food. Improving the ability of ghrelin ligands to penetrate the blood brain barrier would enhance central delivery to GHSR-1a expressing brain regions, particularly within the mesolimbic reward circuitry.

Nanogel-based nasal ghrelin vaccine prevents obesity.

Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein. Ghrelin-PspA antigen was mixed with cyclic di-GMP adjuvant to enhance the immunogenicity and incorporated within a nanometer-sized hydrogel for the effective antigen delivery. Intranasal immunization with ghrelin-PspA vaccine elicited serum immunoglobulin G antibodies against ghrelin and attenuated body weight gain in diet-induced obesity mice. This obesity-attenuating effect was caused by a decrease in fat accumulation and an increase in energy expenditure that was partially due to an increase in the expression of mitochondrial uncoupling protein 1 in brown adipose tissue. The development of this nasal vaccine provides a new strategy for the prevention and treatment of obesity.

Cholinergic neurons in the dorsomedial hypothalamus regulate food intake

ObjectiveCentral cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. MethodsTo selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice. We also generated transgenic mice expressing channelrhodopsins in cholinergic neurons with the Cre-LoxP technique. To delete the Chat gene exclusively in the DMH, we injected an AAV carrying a Cre recombinase transgene into the DMH of floxed ChAT mice. Food intake was measured with and without selective stimulation of DMH cholinergic neurons. ResultsMice lacking the Chat gene in the DMH show reduced body weight as compared to control. Chemogenetic activation of DMH cholinergic neurons promotes food intake. This orexigenic effect is further supported by experiments of optogenetic stimulation of DMH cholinergic neurons. DMH cholinergic neurons innervate pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Treatment with acetylcholine (ACh) enhances GABAergic inhibitory transmission to ARC POMC neurons that is blocked by the muscarinic receptor antagonist. Direct activation of cholinergic fibers in the ARC readily stimulates food intake that is also abolished by the muscarinic receptor antagonist. ConclusionACh released from DMH cholinergic neurons regulates food intake and body weight. This effect is mediated in part through regulation of ARC POMC neurons. Activation of muscarinic receptors on GABAergic axon terminals enhances inhibitory tone to ARC POMC neurons. Hence, this novel DMHACh → ARCPOMC pathway plays an important role in the control of food intake and body weight.

The role of acylated-ghrelin in the regulation of sucrose intake.

The octanoyl modification of ghrelin by ghrelin O-acyltransferase (GOAT) is essential for exerting its physiologic actions. Since exogenous acylated-ghrelin has shown to stimulate food intake in humans and rodents, GOAT has been regarded as a promising target for modulating appetite, thereby treating obesity and diabetes. However, GOAT-knockout (KO) mice have been reported to show no meaningful body weight reduction, when fed a high-fat diet. In this study, we sought to determine whether GOAT has a role in the regulation of body weight and food intake when fed a dietary sucrose. We found that GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, when fed a high-fat + high-sucrose diet. In addition, GOAT KO mice fed a medium-chain triglyceride (MCT) + high-sucrose diet showed a marked resistance to obesity and reduced feed efficiency. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity caused by overconsumption of palatable food.

Activity of etv5a and etv5b genes in the hypothalamus of fasted zebrafish is influenced by serotonin

Serotonin has been implicated in the inhibition of food intake in vertebrates. However, the mechanisms through which serotonin acts has yet to be elucidated. Recently, ETV5 (ets variant gene 5) has been associated with obesity and food intake control mechanisms in mammals. We have analyzed a putative physiological function of the two etv5 paralogous genes (etv5a and etv5b) in neuronal food intake control in adult zebrafish that have been exposed to different nutritional conditions. A feeding assay was established and fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), was applied. Gene expression changes in the hypothalamus were determined using real-time PCR. Fasting induced an up-regulation of etv5a and etv5b in the hypothalamus, whereas increased serotonin levels in the fasted fish counteracted the increase in expression. To investigate potential mechanisms the expression of further food intake control genes was determined. The results show that an increase of serotonin in fasting fish causes a reduction in the activity of genes stimulating food intake. This is in line with a previously demonstrated anorexigenic function of serotonin. Our results suggest that obesity-associated ETV5 has a food intake stimulating function and that this function is modulated through serotonin.

Does eating good-tasting food influence body weight?

Does eating good-tasting food influence body weight? To investigate, we first established some concentrations of sucralose and mineral oil in chow that mice strongly preferred. Then, in Experiment 1, we compared groups of 16 mice fed plain chow (i.e., chow with no additives) to groups fed chow with added (a) sucralose, (b) mineral oil, (c) sucralose and mineral oil, or (d) sucralose on odd days and mineral oil on even days. During a 6-week test, the body weights and body compositions of the five groups never differed. In Experiment 2, we compared groups of 18 mice fed plain chow or plain high-fat diet to groups fed these diets with added sucralose. During a 9-week test, the high-fat diet caused weight gain, but the body weights of mice fed the sucralose-sweetened diets did not differ from those fed the corresponding plain versions. Two-cup choice tests conducted at the end of each experiment showed persisting strong preferences for the diets with added sucralose and/or mineral oil. In concert with earlier work, our results challenge the hypothesis that the orosensory properties of a food influence body weight gain. A good taste can stimulate food intake acutely, and guide selection toward nutrient-dense foods that cause weight gain, but it does not determine how much is eaten chronically.

Duplication of neuropeptide Y and peptide YY in Nile tilapia Oreochromis niloticus and their roles in food intake regulation

In vertebrates, the neuropeptide Y (NPY) family peptides have been recognized as key players in food intake regulation. NPY centrally promotes feeding, while peptide YY (PYY) and pancreatic polypeptide (PP) mediate satiety. The teleost tetraploidization is well-known to generate duplicates of both NPY and PYY; however, the functional diversification between the duplicate genes, especially in the regulation of food intake, remains unknown. In this study, we identified the two duplicates of NPY and PYY in Nile tilapia (Oreochromis niloticus). Both NPYa and NPYb were primarily expressed in the central nervous system (CNS), but the mRNA levels of NPYb were markedly lower than those of NPYa. Hypothalamic mRNA expression of NPYa, but not NPYb, decreased after feeding and increased after 7-days of fasting. However, both NPYa and NPYb caused a significant increase in food intake after an intracranial injection of 50ng/g body weight dose. PYYb, one of the duplicates of PYY, had an extremely high expression in the foregut and midgut, whereas another form of duplicate PYYa showed only moderate expression in the CNS. Both hypothalamic PYYa and foregut PYYb mRNA expression increased after feeding and decreased after 7-days of fasting. Furthermore, the intracranial injection of PYYb decreased food intake, but PYYa had no significant effect. Our results suggested that although the mature peptides of NPYa and NPYb can both stimulate food intake, NPYa is the main endogenous functional NPY for feeding regulation. A functional division has been identified in the duplicates of PYY, which deems PYYb as a gut-derived anorexigenic peptide and PYYa as a CNS-specific PYY in Nile tilapia.

Neuropeptide F stimulates ovarian development and spawning in the female giant freshwater prawn, Macrobrachium rosenbergii, and its expression in the ovary during ovarian maturation cycle

Neuropeptide F (NPF) plays important roles in the regulation of a variety of physiological processes, including stimulation of food intake. At present, there is a current lack of basic knowledge regarding the effect of NPF in the control of female crustacean reproduction. In this study, we investigated expression of NPF in ovaries of female Macrobrachium rosenbergii (Mr) during ovarian development cycle, and its effects on ovarian maturation and spawning. MrNPF-immunoreactivity (-ir) was detected in the ovaries and its levels fluctuated during the ovarian maturation cycle: MrNPF-ir was more intense in the early- and mid-stages of ovarian development, and suddenly decreased in the mature stages. By RT-PCR, MrNPF transcript levels also increased during the early- and middle stages of ovarian development, and suddenly fell at late stage. The prawns were treated with varied doses of MrNPF and the effects were investigated by assessing the ovarian maturation period, oocyte diameter (OD), gonado-somatic index (GSI), and hemolymph vitellogenin (Vg) concentration. MrNPF-treated prawns showed significantly decreased ovarian maturation periods, and increased GSI, OD, and Vg levels compared with those of control groups. MrNPF also caused significantly earlier spawning compared with the control groups, while the mean fecundity between MrNPF-treated prawns and controls did not differ significantly. However, the numbers of eggs per spawn among experimental groups were higher compared with those of the controls. This work provides a novel and useful basic knowledge of NPF on female reproduction in crustaceans, and its possible use in aquaculture for accelerating and enhancing reproduction of the female prawns. Statement of relevanceAlternative techniques to eyestalk ablation to stimulate ovarian maturation in captive prawn broodstock are needed in order to avoid cruel practice on cultured prawns. Attempts have been made in using neurohormones, including neuropeptides to prime female broodstocks to stimulate growth and reproduction to replace the eyestalk ablation. NPF is a neuropeptide known for its control of feeding; however, there is currently no report on the role of NPF in female M. rosenbergii reproduction. We are the first to report the effects of NPF on ovarian maturation and spawning, and its expression and fluctuation in ovaries during the ovarian cycle in the female decapod crustacean. Our findings are novel and the data obtained could be useful for accelerating and enhancing reproduction of the female freshwater prawns.

Food-Restriction Lowers the Acoustic Startle Response in both Male and Female Rats, and, in Combination with Acute Ghrelin Injection, Abolishes the Expression of Fear-Potentiated Startle in Male Rats.

Food restriction has been reported to reduce anxiety-like behaviour in male rats, whereas the effects of food restriction on anxiety in female rats are less clear. Ghrelin is a peptide hormone produced and secreted in the stomach that stimulates food intake and is considered to play a role in reward and emotional responses such as fear expression. Under food restriction, endogenous ghrelin levels increase. In the present study, we examined the effect of moderate food restriction (80% of adlibitum fed weight), with or without an acute application of a small dose of exogenous ghrelin intended to cause an immediate hunger response, on the expression of the acoustic startle reflex (ASR). This was carried out under basal conditions (baseline ASR to 90- and 95-dB noise bursts), and in the presence of a light cue associated with a mild foot-shock, as measured by fear-potentiated startle, which compares the proportional change in ASR in the presence of the conditioned stimulus. The results obtained show that food-restriction reduces basal ASR in both male and female rats, apart from any concomitant change in motor activity, suggesting that food-restriction reduces anxiety levels in both sexes. In addition, the data show that food-restriction reduces fear-potentiated startle in male but not female rats. Acute ghrelin injection, prior to fear-potentiated startle testing, eliminates the expression of fear-potentiated startle in food-restricted male rats alone, suggesting a role for ghrelin in the reduction of fear expression in food-restricted male rats. These data imply that, although food-restriction decreases anxiety in both sexes, learned fear responses remain intact after food-restriction in female but not male rats.

Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation.

Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis.

Lentivirus-mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells.

Ghrelin, an orexigenic peptide, acts via the growth hormone secretagogue receptor (GHSR) to stimulate the release of growth hormone. Moreover, it has a range of biological actions, including the stimulation of food intake, modulation of insulin signaling and cardiovascular effects. Recently, it has been demonstrated that ghrelin has a proliferative and antiapoptotic effects in cancers, suggesting a potential role in promoting tumor growth. However, it remains unknown whether GHSR contributes to colorectal cancer proliferation. In this study, the therapeutic effect of lentivirus‐mediated short hairpin RNA (shRNA) targeting ghrelin receptor 1a (GHSR1a) was analyzed in colorectal cancer cell line SW480 both in vitro and in vivo. Our study demonstrated that ghrelin and GHSR1a are significantly upregulated in cancerous colorectal tissue samples and cell lines. In vitro, human colorectal cancer cell line SW480 with downregulation of GHSR1a by shRNA showed significant inhibition of cell viability compared with blank control (BC) or scrambled control (SC) regardless of the application of exogenous ghrelin. Furthermore, GHSR1a silencing by target specific shRNA was shown capable of increasing PTEN, inhibiting AKT phosphorylation and promoting the release of p53 in SW480 cells. In addition, the effects of GHSR1a knockdown were further explored in vivo using colorectal tumor xenograft mouse model. The tumor weights were decreased markedly in GHSR1α knockdown SW480 mouse xenograft tumors compared with blank control or negative control tumors. Our results suggested that the expression of GHSR1a is significantly correlated with the growth of colorectal cancer cells, and the GHSR1a knockdown approach may be a potential therapy for the treatment of colorectal cancer.

Drosophila SLC5A11 Mediates Hunger by Regulating K+ Channel Activity

Hunger is a powerful drive that stimulates food intake. Yet, the mechanism that determines how the energy deficits that result in hunger are represented in the brain and promote feeding is not well understood. We previously described SLC5A11-a sodium/solute co-transporter-like-(or cupcake) in Drosophila melanogaster, which is required for the fly to select a nutritive sugar over a sweeter nonnutritive sugar after periods of food deprivation. SLC5A11 acts on approximately 12 pairs of ellipsoid body (EB) R4 neurons to trigger the selection of nutritive sugars, but the underlying mechanism is not understood. Here, we report that the excitability ofSLC5A11-expressing EB R4 neurons increases dramatically during starvation and that this increase is abolished in the SLC5A11 mutation. Artificial activation of SLC5A11-expresssing neurons is sufficient to promote feeding and hunger-driven behaviors; silencing these neurons has the opposite effect. Notably, SLC5A11 transcript levels in the brain increase significantly when flies are starved and decrease shortly after starved flies are refed. Furthermore, expression of SLC5A11 is sufficient for promoting hunger-driven behaviors and enhancing the excitability of SLC5A11-expressing neurons. SLC5A11 inhibits the function of the Drosophila KCNQ potassium channel in a heterologous expression system. Accordingly, a knockdown of dKCNQ expression in SLC5A11-expressing neurons produces hunger-driven behaviors even in fed flies, mimicking the overexpression of SLC5A11. We propose that starvation increases SLC5A11 expression, which enhances the excitability of SLC5A11-expressing neurons by suppressing dKCNQ channels, thereby conferring the hunger state.

Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice.

Tributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen- inducing adipogenetic gene transcription for adipocyte differentiation. In a previous study, we demonstrated that acute administration of TBT induces c-fos expression in the arcuate nucleus. Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake. In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1-LacZ transgenic mice] for 4weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT-treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1-related β-galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake.

Effects of ghrelin in energy balance and body weight homeostasis.

Ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, GHSR1a, was also identified. Ghrelin, the endogenous ligand for the GH secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). Ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O-acyltransferase enzyme (GOAT). The literature even mentions an extremely complex ghrelin/GOAT/GHSR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers.

Role of the vagus nerve in the development and treatment of diet-induced obesity.

This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie-rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high-fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade-induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity.

How hypothalamus senses and stimulates food intake

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Stimulatory Effect of Cerebral Intraventricular Injection of cNPY on Precocial Feeding Behavior in Neonatal Chicks (Gallus domesticus).

Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in many animals. Most of the supporting evidence for the effects of NPY has been gathered in mammalian species using porcine NPY. To investigate the effects of NPY on precocial feeding initiation in chicks, we firstly used chicken NPY (cNPY) to study its role in food intake and spontaneous activities in 3-day-old male chicks. Food intake was monitored at different times after intracerebroventricular (ICV) injection of cNPY (2.5, 5.0 or 10.0 μg/10 μL) and anti-cNPY antibody (anti-cNPY) (1:9000, 1:3000 or 1:1000 in dilution). cNPY given at different doses significantly increased food intake at 30 min, 60 min, 90 min and 120 min after injection. Chicks treated with 5.0 μg/10 μL of cNPY showed a maximal 4.48 fold increase in food intake comparing to the control at 30 min. There is still more than 2 fold increase in food intake at 120 min after injection of cNPY. Food intake was significantly inhibited by a single ICV injection of anti-cNPY diluted to 1:9000 (60% inhibition), 1:3000 (92% inhibition), and 1:1000 (95% inhibition) at 30 min with 1:1000 being the maximally effective concentration. The inhibitory effects of anti-cNPY (diluted to1:9000, 1:3000, 1:1000) at 120 min post ICV injection were 22%, 42% and 46%, respectively. But ICV of anti-cNPY (1:3000 in dilution) did not block the orexigenic effect of 2.5 μg/10 μL of cNPY. ICV injection of different concentrations of cNPY increases locomotor activity in a dose-dependent manner while ICV anti-cNPY greatly decreased the distance moved by each chick compared to control groups. Taken together, our results demonstrated that cNPY has a promoting effect on chick food intake and locomotor activity, and that endogenous cNPY might play a positive role in regulating precocial feeding behavior in newly hatched chicks.

Identification of Novel Probiotics to Modify Appetite and Satiety Directly Targeting the Ghrelin Receptor

Ghrelin is a stomach‐derived peptide that acts as orexigenic hormone in the hypothalamus stimulating food intake through the growth hormone secretagogue receptor (GHS‐R1a). Dysregulated ghrelin signalling may contribute to the development of metabolic disorders such as obesity. Current pharmacologic anti‐obesity treatments lack efficacy and have shown severe side effects, highlighting the urgent need for novel strategies contributing to the maintenance of a healthy weight.Natural products are receiving special consideration as sources of bioactives with beneficial health effects which may be safer for consumers than synthetic therapeutics. One of the most investigated natural bioactives are live microorganisms with health benefit effects, also known as probiotics. Thus, food products containing probiotics are receiving increased scientific and commercial focus in recent years. These probiotic‐mediated beneficial effects on human health are due to changes in the gut microbiota via oral delivery of viable strains of bacteria that are then integrated into the gut system. Gut microbiota ferment nutrients and secrete bioactive compounds inducing several responses within the intestinal mucosa and controlling the gut's barrier and endocrine functions.In this study we investigate the ability of different probiotic bacteria to modulate the GHS‐R1a receptor. Bacteria were cultured overnight under anaerobic conditions at 37°C. Culture supernatants were collected by centrifugation, resuspended in 1× Hanks balanced salt solution containing 20mM HEPES, and incubated in anaerobiosis for 4 h. Afterwards, supernatants were used to investigate the probiotics ghrelin receptor activation potential by calcium mobilization and receptor internalization assays in human embryonic kidney cells (Hek) stably expressing the GHS‐R1a receptor.Different Lactobacillus and Bifidobacterium strains with ability to modulate the ghrelin receptor have been identified. Future investigations, including identification of the bioactives present in the probiotic supernatants as well as in vivo studies supporting these findings, are needed in order to confirm their potential as anti‐obesity therapeutics.Support or Funding InformationWork funded by CREMO SA

The role of ghrelin in the regulation of glucose homeostasis.

Ghrelin is a 28-amino acid (aa) stomach-derived peptide discovered in 1999 as the endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Ghrelin-producing cells constitute a distinct group of endocrine cells dispersed throughout the gastric mucosa and to a lesser extent in the small intestine and the endocrine pancreas. Ghrelin plasma levels rise during fasting and chronic caloric restriction to stimulate food intake and fat storage and to prevent life-threatening falls in blood glucose. Plasma ghrelin levels decrease after a meal is consumed and in conditions of energy surplus (such as obesity). Ghrelin has emerged as a key player in the regulation of appetite and energy homeostasis. Ghrelin achieves these functions through binding the ghrelin receptor GHS-R in appetite-regulating neurons and in peripheral metabolic organs including the endocrine pancreas. Ghrelin levels are negatively correlated with body mass index (BMI) and insulin resistance. In addition, ghrelin secretion is impaired in obesity and insulin resistance. Several studies highlight an important role for ghrelin in glucose homeostasis. Genetic, immunological, and pharmacological blockade of ghrelin signaling resulted in improved glucose tolerance and insulin sensitivity. Furthermore, exogenous ghrelin administration was shown to decrease glucose-induced insulin release and increase glucose level in both humans and rodents. GHS-R was shown to be expressed in pancreatic β-cells and ghrelin suppressed insulin release via a Ca2+-mediated pathway. In this review, we provide a detailed summary of recent advances in the field that focuses on the role of insulin and insulin resistance in the regulation of ghrelin secretion and on the role of ghrelin in glucose-stimulated insulin secretion (GSIS).