Food Intake In Mammals Research Articles

Thyrotropin-Releasing Hormone and Food Intake in Mammals: An Update.

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food intake is not well understood. We review studies demonstrating that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence points to TRH neurons that are prime candidate vectors for TRH action on food intake. These include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food intake control in each anatomical scene.

Linking stress with urocortin in rats.

The corticotropin-releasing factor neuropeptides (CRH and UCN-1,2,3), as well as spexin, contribute to the control of energy balance and limit food intake in mammals. However, the role of these neuropeptides in chronic variable stress remains unknown. The effect of chronic varied stress on circulating corticosterone levels and urocortin expression levels in the brains of experimental rats was studied in this study. Rats were subjected with 28 days long term stress protocol, end of stress protocol experimental and control animal organs isolated, brain urocorcortin-1,2,3 expression by RT-PCR and serum corticosterone by ELISA method. UCN levels in the brain were altered in rats subjected to prolonged varied stress. Furthermore, corticosterone levels were elevated as a result of the same urocortin expression pattern, indicating that urocortin expression is controlled by glucocorticoids via a glucocorticoid-responsive element (GRE). Thus, data shows that hypothalamus-pituitary-adrenal (HPA) axis, also known as the LHPA axis, and limbic system are both stimulated by stress, which is reflected in the form of elevated corticosterone levels, according to the genes UCN1, 2, and 3.

Insights on discovery, efficacy, safety and clinical applications of ghrelin receptor agonist capromorelin in veterinary medicine.

Growth hormone and insulin like growth factor-1 plays an important role in the regulation of body composition and metabolism. Growth Hormone is released from the pituitary through a specific G-protein coupled receptor (GPCR) called growth hormone secretagogue receptor 1a expressed in the hypothalamus. Ghrelin is a peptide hormone released from the cells in the stomach, which stimulates appetite and food intake in mammals, regulates gut motility, gastric acid secretion, taste sensation, circadian rhythm, learning and memory, oxidative stress, autophagy, glucose metabolism etc. When the release of the endogenous ligand GHSR-1a, i.e., ghrelin is malfunctioned or stopped, external substitutes are administrated to induce the stimulation of growth hormone and appetite. A class of compound known as ghrelin receptor agonists are developed as an external substitute of ghrelin for regulation and stimulation of growth hormone in frailty, for body weight gain, muscle mass gain, prevention of cachexia and for the treatment of chronic fatigue syndromes. Capromorelin [Entyce™ (Aratana Therapeutics, Leawood, KS, USA)] is the only FDA (Food and Drug Administration) approved (May 2016) drug used for stimulating appetite in dogs and was marketed in the fall of 2017. In 2020, USFDA approved Capromorelin [Elura™ (Elanco US Inc.)] for the management of weight loss in chronic kidney disease of cats. This article reviews the discovery of the ghrelin receptor agonist capromorelin, its efficacy, safety, clinical applications and aims to delineate its further scope of use in veterinary practice.

Neuromedin U regulates food intake of Siberian sturgeon through the modulation of central and peripheral appetite factors.

Neuromedin U (NMU) has a critical function on the regulation of food intake in mammals, while the information is little in teleost. To investigate the function of NMU on appetite regulation of Siberian sturgeon (Acipenser baerii), this study first cloned nmu cDNA sequence that encoded 154 amino acids including NMU-25 peptide. Besides, the results showed that nmu mRNA was widely distributed in various tissues especially in the hypothalamus and telencephalon. The results of nutritional status (pre-feeding and post-feeding, fasting and re-feeding) experiments showed that nmu mRNA expression was significantly decreased at 1 and 3 h after feeding in different brain regions. Similarly, after feeding, the expression of nmu significantly decreased in peripheral tissues. Moreover, nmu expression in the hypothalamus was significantly increased after fasting 1 d, but decreased after fasting 17 d, which was significantly reversed after re-feeding. However, other brain regions like telencephalon and peripheral tissues like oesophagus, intestinum valvula and liver have different change patterns. Further study showed that acute i.c.v. and i.p. injection of NMU and chronic i.p. injection of NMU significantly reduced the food intake in a dose-dependent mode. In addition, the expressions of several critical appetite factors (nmu, aplein, cart, cck, ghrelin, npy, nucb2, pyy and ucn3) were significantly affected by acute NMU-25 administration in the hypothalamus, intestinum valvula and liver. These results indicate that NMU-25 has the anorexigenic function on food intake by affecting different appetite factors in Siberian sturgeon, which provides a foundation for further exploring the appetite regulation networks in fish.

GLP-1 responds to postprandial hyperglycemia by reducing transcription level in grass carp (Ctenopharyngodon idella)

Glucagon-like peptide-1 (GLP-1), a member of the proglucagon derived peptide family, is a highly effective incretin to reduce plasma glucose and inhibit food intake in mammals. The physiological function of GLP-1 has been elucidated in some ‘glucose intolerant’ carnivorous fishes. To lay a better understanding in fish glucose intolerance, we synthesized homologous GLP-1 peptide and explored its roles in appetite and glucose regulation under intraperitoneal (IP) injection in herbivorous grass carp which has higher glucose intolerance. The results showed that GLP-1 increased plasma glucose in grass carp. The hyperglycemic effect of the fish GLP-1 was mainly through promoting gluconeogenesis, accompanied by inhibition of glycogen synthesis and stimulation of glycogenolysis pathway. In addition, GLP-1 upregulated the expression of anorexigenic gene (cart) and decreased the orexigenic genes (npy and agrp) expression in grass carp hypothalamus as a conservative way to inhibit the appetite under GLP-1 injection after 2 h. Taken together, the hyperglycemic effect and anorectic role of GLP-1 were performed in a basically consistent manner across fishes with different food habits. What’s more, the gene expressions of proglucagon yielded GLP-1 in foregut and hindgut of grass carp were significantly decreased after a meal within 24 h, indicating that fish might suppress the accumulation of plasma glucose by decreasing GLP-1 expression in a unique way to herbivorous fish. Therefore, this study provided a new perspective for illustrating the difference in glucose utilization among fishes with different food habits based on GLP-1.

Circulating levels of urocortin neuropeptides are impaired in children with overweight

ObjectiveThe corticotropin‐releasing factor neuropeptides (corticotropin‐releasing hormone [CRH] and urocortin [UCN]‐1,2,3) and spexin contribute to the regulation of energy balance and inhibit food intake in mammals. However, the status of these neuropeptides in children with overweight has yet to be elucidated. This study investigated the effect of increased body weight on the circulating levels of these neuropeptides.MethodsA total of 120 children with a mean age of 12 years were enrolled in the study. Blood samples were collected to assess the circulating levels of neuropeptides and were correlated with various anthropometric, clinical, and metabolic markers.ResultsPlasma levels of UCNs were altered in children with overweight but less so in those with obesity. Furthermore, the expression pattern of UCN1 was opposite to that of UCN2 and UCN3, which suggests a compensatory effect. However, no significant effect of overweight and obesity was observed on CRH and spexin levels. Finally, UCN3 independently associated with circulating zinc‐alpha‐2‐glycoprotein and UCN2 levels, whereas UCN1 was strongly predicted by TNFα levels.ConclusionsSignificant changes in neuropeptide levels were primarily observed in children with overweight and were attenuated with increased obesity. This suggests the presence of a compensatory mechanism for neuropeptides to curb the progression of obesity.

Neuropeptide S (NPS) and its receptor (NPSR1) in chickens: cloning, tissue expression, and functional analysis

Neuropeptide S (NPS) and its receptor neuropeptide S receptor 1 (NPSR1) have been suggested to regulate many physiological processes in the central nervous system (CNS), such as arousal, anxiety, and food intake in mammals and birds, however, the functionality and tissue expression of this NPS-NPSR1 system remain unknown in birds. Here, we cloned NPS and NPSR1 cDNAs from the chicken brain and reported their functionality and tissue expression. The cloned chicken NPS is predicted to encode a mature NPS peptide of 20 amino acids, which shows a remarkable sequence identity (∼94%) among tetrapod species examined, while NPSR1 encodes a receptor of 373 amino acids conserved across vertebrates. Using cell-based luciferase reporter systems, we demonstrated that chicken NPS could potently activate NPSR1 expressed in vitro and thus stimulates multiple signaling pathways, including calcium mobilization, cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, indicating that NPS actions could be mediated by NPSR1 in birds. Quantitative real-time PCR revealed that NPS and NPSR1 are widely expressed in chicken tissues, including the hypothalamus, and NPSR1 expression is likely controlled by a promoter upstream exon 1, which shows strong promoter activities in cultured DF-1 cells. Taken together, our data provide the first proof that the avian NPS-NPSR1 system is functional and helps to explore the conserved role of NPS and NPSR1 signaling in tetrapods.

A newly discovered interference of the central nitrergic system on oxytocin-induced hypophagia in layer-type chickens

Various neurochemical pathways are participating in the regulation of food intake in mammals and birds. Both oxytocin (OT) and nitric oxide (NO) are known as hypophagic agents in birds. This study consisted of 6 experiments and each experiment had 4 groups (ngroup=11, 5-day-old chickens). In all experiments, 3-hour food-deprived (FD3) birds received intracerebroventricular (ICV) injections either control diluent or drug solution. Then the birds had ad libitum access to the food and fresh water and then cumulative food intake (gr) was measured based on the percentage of the body weight (%BW). In experiments 1 to 3, ICV injections of L-arginine (precursor of NO, 200, 400, and 800 nmol), L-NAME (NOS inhibitor, 100, 200, and 400 nmol) and OT (2.5, 5, and 10 µg) were performed respectively. In experiment 4, each group received any ICV injections of L-NAME (100 nmol), OT (10 µg) or a co-injection of L-NAME (100 nmol) and OT (10 µg). In experiment 5, L-arginine (ICV, 200 nmol), OT (10 µg), or L-arginine (200 nmol) and OT (10 µg) were injected to the groups. Experiment 6 was similar to the experiment 5, although the dose of OT was 2.5 µg in all the treatment groups. Results showed that the ICV injection of L-NAME (100 nmol) significantly attenuated hypophagic effect induced by OT (10 µg) (p < 0.05). Findings suggested that NO might mediate the hypophagic effect of OT in FD3 neonatal layer-type chickens.

The anorexigenic effect of neuropeptide AF in Japanese quail, Coturnix japonica, is associated with activation of the melanocortin system

Neuropeptide AF (NPAF) decreases food and water intake in birds and food intake in mammals. In this study, the objective was to determine the effects of centrally administered NPAF on food and water intake, hypothalamic c-Fos immunoreactivity and hypothalamic mRNA abundance of appetite-regulating factors in Japanese quail (Coturnix japonica). Seven days post hatch, 6 h fasted quail were intracerebroventricularly (ICV) injected with 0 (vehicle), 4, 8, or 16 nmol of NPAF and food and water intake were measured at 30 min intervals for 180 min. In Experiment 1, chicks which received 4, 8, and 16 nmol ICV NPAF had reduced food intake for 120, 60 and 180 min following injection, respectively, and reduced water intake during the entire 180 min observation. In Experiment 2, there was increased c-Fos immunoreactivity in the paraventricular nucleus, the ventromedial nucleus of the hypothalamus, and the dorsomedial hypothalamic nucleus in NPAF-injected quail. In Experiment 3, ICV NPAF was associated with decreased corticotropin-releasing factor mRNA, and an increase in hypothalamic proopiomelanocortin and melanocortin receptor 4 mRNA. These results demonstrate that central NPAF suppresses food and water intake in quail, effects that are likely mediated via the melanocortin system in the hypothalamus.

SAT-603 Growth Hormone-Releasing Hormone (GHRH) Antagonists Stimulate Feeding in Mice

Growth hormone-releasing hormone (GHRH) is a hypothalamic neuropeptide which stimulates the synthesis and secretion of growth hormone (GH) in pituitary gland. GHRH was also found to modulate food intake in mammals. MIA-690 is a synthetic GHRH antagonist of the Miami (MIA) series with potent antitumor effects. To date, its role in hypothalamic feeding modulation has not been evaluated. In the present study, we aimed to investigate the effects of chronic MIA-690 administration on feeding behavior, locomotor activity and hypothalamic dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), orexigenic peptides [agouti-related peptide (AgRP) and neuropeptide Y (NPY)] and anorexigenic peptides [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] activity.Adult C57/BL6 mice were treated daily for 4 weeks by subcutaneous administration of (5 µg) MIA-690 or vehicle solution. Food intake and body weight were recorded every 4 days throughout the study. Immediately after the last injection, locomotor activity in the home cage was recorded, and thereafter animals were sacrificed. Visceral, subcutaneous and brown fat depots were quickly excised and weighed. Hypothalamus was also dissected for evaluating gene expression of AgRP, NPY, CART and POMC by real-time reverse transcription polymerase chain reaction. In addition, hypothalamic DA, NE and 5-HT levels were measured by high performance liquid chromatography (HPLC) coupled to electrochemical detection.Our findings show that administration of MIA-690 increased food intake and body weight, without affecting locomotor activity. No difference was observed in visceral, subcutaneous and brown fat mass in animals treated with MIA-690 or vehicle. As for neuromodulatory effects, a significant increase of AgRP gene expression and NE levels, along with a reduction of 5-HT levels were found after MIA-690 treatment. On the other hand, we did not observe any alteration in NPY, POMC and CART gene expression, as well as DA levels, following MIA-690 administration.In conclusion, chronic peripheral administration of MIA-690 could play an orexigenic role paralleled by increased body weight. The stimulation of feeding could be mediated, at least in part, by increased AgRP gene expression and NE levels and decreased 5-HT levels, in the hypothalamus.

Central microinjection of phytohormone abscisic acid changes feeding behavior, decreases body weight, and reduces brain oxidative stress in rats

Objectives: Natural products have a potential role on food intake in mammals. It has been reported that phytohormone abscisic acid (ABA) has a regulatory role on metabolic processes. Here, the effects of ABA on feeding behavior and brain oxidative stress were investigated in male Wistar rats.Methods: ABA was injected intracerebroventricularly. Experimental groups were included (n = 9): control (received no injection), ABA vehicle (received normal saline), and ABA-treated groups were injected with different doses of ABA (2.5, 5, and 10 μg/rat for 7 days). Daily cumulative daytime and nighttime food consumption, meal frequency, meal duration, and alteration in body weight were recorded. At the end of behavioral experiment, catalase and peroxidase activity and malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were assayed.Results: The results showed that ABA (5 and 10 μg) increased the meal frequency. Moreover, ABA could decrease body weight and MDA and H2O2 levels and increased the catalase and peroxidase activities in diencephalon. It also decreased the MDA concentration in the brain stem.Discussion: Taken together, ABA has an important effect on feeding behavior and body weight in rats likely via increasing antioxidant capacity. However, further studies are still required to determine the underlying mechanisms of ABA on the feeding behavior.

Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs.

Ghrelin is a hormone, secreted from cells in the stomach, which is important in the regulation of appetite and food intake in mammals. It exerts its action by binding to a specific G‐protein‐coupled receptor, the growth hormone secretagogue receptor 1a (GHS‐R1a) which is found in areas of the brain associated with the regulation of food intake. Ghrelin causes a release of growth hormone (GH) through binding to GHS‐R1a in the hypothalamus and pituitary gland. A class of compounds known as growth hormone secretagogues, or ghrelin receptor agonists, were developed for therapeutic use in humans for the stimulation of GH in the frail elderly, and have subsequently been studied for their effects on increasing appetite and food intake, increasing body weight, building lean muscle mass, and treating cachexia. Subsequent research has shown that ghrelin has anti‐inflammatory and immunomodulatory effects. This article reviews the basic physiology of ghrelin and the ghrelin receptor agonists, including the available evidence of these effects in vitro and in vivo in rodent models, humans, dogs and cats. One of these compounds, capromorelin, has been FDA‐approved for the stimulation of appetite in dogs (ENTYCE ®). The data available on the safety and effectiveness of capromorelin is reviewed, along with a discussion of the potential clinical applications for ghrelin receptor agonists in both human and veterinary medicine.

Brain and intestinal expression of galanin-like peptide (GALP), galanin receptor R1 and galanin receptor R2, and GALP regulation of food intake in goldfish (Carassius auratus)

Galanin-like peptide (GALP) is a 60 amino acid neuropeptide originally discovered from porcine hypothalamus, and is involved in the regulation of food intake in mammals. Since its discovery, GALP and its receptors (GALR1 and GALR2) have been characterized in mammals, but no publications are available on GALP in fish and other non-mammals. The present study aimed to characterize brain and intestinal GALP and its receptors using immunohistochemistry in a teleost, the goldfish (Carassius auratus), and to study its effects on feeding behavior. Immunostaining of brain sections shows the presence of GALP- and GALR1- and GALR2-like immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, the optic tectum, the torus longitudinalis and the cerebellum. Signal for GALP was also observed in the fasciculus retroflexus. In the gut, GALP-and GALR1 and GALR2 immunoreactive cells were detected in the mucosa. Results from the feeding study demonstrate that intracerebroventricular administration of GALP (1ng/g bodyweight) increases goldfish food intake at 1h post-injection. These observations form the first report on the presence of GALP in the fish brain and gut, and also on its modulatory role on fish feeding behavior. GALP, as in mammals, appears to be a functional neuropeptide in goldfish.

Ghrelin in Senegalese sole (Solea senegalensis) post-larvae: Paracrine effects on food intake

Successful food consumption and digestion depend on specifics anatomical and behavioral characteristics and corresponding physiological functions that should be ready to work at the appropriate time. The physiological regulation of appetite and ingestion involves a complex integration of peripheral and central signals by the brain. Ghrelin is a peptide hormone involved in the control of energy homeostasis and increases food intake in mammals, however ghrelin has species-specific actions on food intake in fish. The aim of this study was to investigate whether this peptide has an orexigenic or anorexigenic role in Senegalese sole (Solea senegalensis) in order to improve the knowledge of the physiological basis underlying feeding activity. Feed intake was measured at several sampling points to determine the overall action time of the peptide and its effect in Senegalese sole food intake. Artemia protein digestibility and retention were determined in order to analyze the ghrelin effect in fed and fasted Senegalese sole post-larvae. Results suggested that ghrelin acts as orexigenic hormone in Senegalese sole, with a response time around 25min. Results indicated that Senegalese sole post-larvae are able to maintain absorption and retention capacities independently of feeding rate and nutritional status. Furthermore, the present study gives insight for the first time of the fate of the retained amino acids, being mainly used for protein accretion (86.79% of retained amino acids recovered in protein and FAA fractions).

Possible Involvement of Beta-Adrenergic Receptors on Nociceptin/Orphanin FQ Induced Food Consumption in Male Rats

Background: The nociceptin/orphanin FQ (N/OFQ) peptide is the endogenous ligand for the N/OFQ peptide (NOP) receptor. Beta adrenergic receptors and N/OFQ are involved in the regulation of food intake through central and peripheral mechanisms. Objectives: The aim of this study was to determine the possible interaction between beta adrenergic and N/OFQ receptors on food consumption in male rats. N/OFQ agonists have been shown to increase food intake in mammals and birds. Beta adrenergic receptors physiologically inhibit food intake in mammals. Methods: In this experimental study were used male rats (250-300 g). In first two experiments, rats received intraperitoneal injections of isoproterenol (0, 0.5, 1 and 2 mg/kg) and Nociceptin agonist 64 - 6198 (0, 1, 2 and 4 mg/kg) respectively. In third experiment 64 - 6198 (4 mg/kg) and (2 mg/kg) isoproterenol were injected. In experiments 4 effects of isoproterenol (0.5 mg/kg) and Nociceptin antagonist (8 mg/kg) on food consumption was investigated. Latency time to feeding was examined in experiment 5. The data were statistically analyzed using One-way ANOVA and Tukey test. Results: Latency time to feeding increased and decreased by isoproterenol and nociceptin/orphanin, respectively. Administration of N/OFQ increased cumulative food intake in rats (P < 0.05). The i.p. injection of isoproterenol decreased food intake and also the hyperphagic effect of N/OFQ agonist is inhibited by isoproterenol, whereas sub-anorectic doses of isoproterenol and N/OFQ antagonist synergistically attenuated cumulative feed consumption when combined (P < 0.01). Conclusions: On the basis of these findings, it can be concluded that isoproterenol may decrease food intake in rats by reduction in the N/OFQ content.

Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response

Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase infood and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.

Methylamine induced hypophagia is mediated via dopamine D1 and D2 receptors in neonatal meat chicks.

Recently, methylamine has been found as an endogenous amine, which is controlling food intake in mammals. However, there is no evidence about the effect of methylamine on feeding behavior in poultry. So, the present study was designed to evaluate the effect of intracerebroventricular (ICV) injection of methylamine and involvement of central methylamine/dopaminergic systems on feeding behavior in neonatal meat type chicks. In experiment 1, chicks were ICV injected with different doses of methylamine (0.48, 0.96, 1.44, 1.92 and 2.40 μmol). In experiment 2, chicks received a dose of either the control solution, 2.40 μmol methylamine, 125 nmol L-DOPA (dopamine precursor) or a combination of methylamine plus L-DOPA. Experiments 3-7 were similar to experiment 2 except that 150 nmol 6-OHDA (dopamine synthase inhibitor), 5 nmol SCH23390 (D1 receptor antagonist), 5 nmol AMI-193 (D2 receptor antagonist), 6.4 nmol NGB2904 (D3 receptor antagonist) and 6 nmol L-741, 742 (D4 receptor antagonist) were used instead of 125 nmol L-DOPA, respectively. Cumulative food intake was determined until 2 h post-injection. According to the results, methylamine significantly decreased food intake in a dose dependent manner (p < 0.05). The inhibitory effect of methylamine on food intake was significantly attenuated by 6-OHDA, SCH23390 and AMI-193 (P < 0.05), but NGB2904 and L-741, 742 had no effect on food intake induced by methylamine. In addition, hypophagic effect of methylamine significantly amplified by L-DOPA (P < 0.05). These results suggest that methylamine decrease food intake and there is an interaction between methylamine and dopaminergic system via D1 and D2 receptors in chickens.

Role of the Oxytocin Receptor Expressed in the Rostral Medullary Raphe in Thermoregulation During Cold Conditions.

Recent papers have reported that oxytocin (Oxt) and the oxytocin receptor (Oxtr) may be involved in the regulation of food intake in mammals. We therefore suspected the Oxt/Oxtr system to be involved in energy homeostasis. In previous studies, we found a tendency toward obesity in Oxtr-deficient (Oxtr−/−) mice, as well as impaired thermoregulation when these mice were exposed to cold conditions. In the present study, we observed the expression of Oxtr in the rostral medullary raphe (RMR), the brain region known to control thermogenesis in brown adipose tissue (BAT). Through immunohistochemistry, we detected neurons expressing Oxtr and c-Fos in the RMR of mice exposed to cold conditions. Up to 40% of Oxtr-positive neurons in RMR were classified as glutamatergic neurons, as shown by immunostaining using anti-VGLUT3 antibody. In addition, mice with exclusive expression of Oxtr in the RMR were generated by injecting an AAV-Oxtr vector into the RMR region of Oxtr−/− mice. We confirmed the recovery of thermoregulatory ability in the manipulated mice during exposure to cold conditions. Moreover, mice with RMR-specific expression of Oxtr lost the typical morphological change in BAT observed in Oxtr−/− mice. Additionally, increased expression of the β3-adrenergic receptor gene, Adrb3, was observed in BAT. These results are the first to show the critical role of RMR Oxtr expression in thermoregulation during cold conditions.

The novel SNPs of leptin gene and their associations with growth traits in Chinese Nanjiang Yellow goat

The leptin (LEP) gene encodes a protein that greatly affects the regulation of body weight, energy balance, and food intake in mammals. The objective of the present work was to identify genetic variants of the caprine LEP gene in 411 individuals from five Chinese goat breeds. Six novel single nucleotide polymorphisms (SNPs) (g.117T>C, g.1642G>A, g.2883G>A, g.3053T>C, g.3190G>A, and g.3314T>C) were detected using DNA sequencing. A chi-squared (χ2) test showed that all of the LEP SNPs were in Hardy–Weinberg equilibrium in the studied population (P>0.05). Six common haplotypes were identified in the five goat populations, with frequencies ranging from 0.083 to 0.244. The r2 linkage disequilibrium plot of the LEP SNPs indicated linkage disequilibrium only in the cultured breeds (NJ and JY). Statistical analysis revealed that all of the six SNPs of the LEP gene were associated with growth traits. The individuals with the GG genotype at g.1642G>A and g.3190G>A loci showed higher birth weight (2.38±0.03, 2.43±0.05) and weight at 2months of age (10.59±0.16, 10.71±0.26) than the A-bearing genotypes (AA or GA, P<0.05). Our findings indicate that polymorphisms of the caprine LEP gene might be important genetic factors influencing growth traits, and these genetic markers may be useful for future marker-assisted selection programs in goat breeding and production.

Central regulation of food intake in mammals and birds: a review

Appetite regulates by a complex system of central and peripheral signals which interact in order to modulate ingestion response. A number of peptides comprise a complex network that regulates feeding behavior in vertebrates. This review is focused on the main neurotransmitters and peptides that influence feeding responses in mammals and birds. On the basis of literature review, there are several evidences that neurotransmitters have different effects on food intake between mammals and birds. Also, central regulation of food intake regulates via different mechanisms in animals. So, the aim of this review was to investigate comparative food-intake regulation mechanisms in mammals and birds.