RESUMO
Nucleobindin2 (NUCB2) is a member of nucleobindin family which was first found in the nucleus of the hypothalamus, and had a relationship in diet and energy homeostasis. Its location in normal tissues such as stomach and islet further confirms that it plays a vital role in the regulation of physiological functions of the body. Besides, NUCB2 participates in tumorigenesis through activating various signal-pathways, more and more studies indicate that NUCB2 might impact tumor progression by promoting or inhibiting proliferation, apoptosis, autophagy, metastasis, and invasion of tumor cells. In this review, we comprehensively stated NUCB2's expression and functions, and introduced the role of NUCB2 in physiology and pathology and its mechanism. What is more, pointed out the potential direction of future research.
Assuntos
Proteínas de Ligação ao Cálcio , Proteínas do Tecido Nervoso , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Hipotálamo/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , NucleobindinasRESUMO
Obesity is a mild chronic inflammation that causes many metabolic diseases. It was aimed to investigate some parameters affective on the energy metabolism by adding zinc (Zn, ZnSO4) to drinking water of diet-induced obese rats. Five-week aged, male Sprague Dawley rats divided into as control group, consuming standard rat diet, and high-fat diet (HFD) group. After obesity induced by feeding HFD for 8 weeks, the obese rats were divided into Zn-supplemented obese group (HFD + obese + Zn; 150 mg Zn/L (for 6 weeks), 235 mg Zn/L (7th week), 250 mg Zn/L (8th week) in drinking water) and obese group (HFD + obese). Mean body weight, serum concentrations of C-reactive protein, neuropeptide-Y, leptin, insulin fasting blood glucose, and HOMA-IR were statistically decreased by given Zn in HFD + obese + Zn group compared to HFD + obese rats. It was observed that the total cholesterol, LDL, and HDL cholesterol levels of HFD + obese + Zn group became closer to the control group level, and Zn supplementation caused a statistically significant decrease in cholesterol profile than HFD + obese rats. Also, increased mean serum nesfatin-1 level, an effective protein for the formation of satiety, was analyzed in HFD + obese + Zn group when compared to HFD + obese ones. Serum triglyceride concentration tended to decrease with the effect of Zn in obese rats. In conclusion, it can be said that oral use of Zn could improve energy balance and prevent the occurrence of metabolic diseases related to obesity depending on the anti-inflammatory effect of Zn.
Assuntos
Obesidade , Zinco , Animais , Proteína C-Reativa , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Água Potável , Leptina , Masculino , Neuropeptídeo Y , Nucleobindinas , Obesidade/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Zinco/farmacologiaRESUMO
Ghrelin and nesfatin-1 are enteroendocrine peptide hormones expressed in rat X/A-like and human P/D1cells of the gastric mucosa. Besides their effect on food intake, both peptides are also implicated in various other physiological systems. One of these is the reproductive system. This present review illustrates the distribution of ghrelin and nesfatin-1 along the hypothalamus-pituitary-gonadal (HPG) axis, their modulation by reproductive hormones, and effects on reproductive functions as well as highlighting gaps in current knowledge to foster further research.
Assuntos
Grelina/metabolismo , Nucleobindinas/metabolismo , Reprodução/genética , Feminino , Grelina/sangue , Grelina/genética , Humanos , Hipotálamo/metabolismo , Nucleobindinas/sangue , Nucleobindinas/genética , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , GravidezRESUMO
Background: Nesfatin-1 is an 82-amino acid polypeptide, cleaved from the 396-amino acid precursor protein nucleobindin-2 (NUCB2) and discovered in 2006 in the rat hypothalamus. In contrast to the growing body of evidence for the pleiotropic effects of the peptide, the receptor mediating these effects and the exact signaling cascades remain still unknown. Methods: This systematic review was conducted using a search in the Embase, PubMed, and Web of Science databases. The keywords "nesfatin-1" combined with "receptor", "signaling", "distribution", "pathway", g- protein coupled receptor", and "binding" were used to identify all relevant articles reporting about potential nesfatin-1 signaling and the assumed mediation via a Gi protein-coupled receptor. Results: Finally, 1,147 articles were found, of which 1,077 were excluded in several steps of screening, 70 articles were included in this systematic review. Inclusion criteria were studies investigating nesfatin-1's putative receptor or signaling cascade, observational preclinical and clinical studies, experimental studies, registry-based studies, cohort studies, population-based studies, and studies in English language. After screening for eligibility, the studies were assigned to the following subtopics and discussed regarding intracellular signaling of nesfatin-1 including the potential receptor mediating these effects and downstream signaling of the peptide. Conclusion: The present review sheds light on the various effects of nesfatin-1 by influencing several intracellular signaling pathways and downstream cascades, including the peptide's influence on various hormones and their receptors. These data point towards mediation via a Gi protein-coupled receptor. Nonetheless, the identification of the nesfatin-1 receptor will enable us to better investigate the exact mediating mechanisms underlying the different effects of the peptide along with the development of agonists and antagonists.
Assuntos
Hipotálamo/metabolismo , Nucleobindinas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Humanos , Transdução de Sinais/fisiologiaRESUMO
Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.
Assuntos
Proteínas de Peixes/metabolismo , Carpa Dourada/metabolismo , Hipotálamo/metabolismo , Rim/metabolismo , Nucleobindinas/metabolismo , Hipófise/metabolismo , Animais , Células Cultivadas , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Proteínas de Peixes/genética , Carpa Dourada/genética , Masculino , Nucleobindinas/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Restrição FísicaRESUMO
BACKGROUND: Fibrinogen and interleukin-1ß as a proinflammatory cytokine and interleukin-10 and nesfatin-1 as an anti-inflammatory cytokine have an important role in the development and prevention of systemic inflammation and incidence of obesity-induced diseases. Thus, this study is aimed at the interaction effects of aerobic training and oak husk hydroalcoholic extract consumption on plasma levels of fibrinogen, interleukin-1ß, nesfatin-1, and interleukin-10 in obese elderly male mice. MATERIALS AND METHODS: In this experimental study, 40 fat male mice were fed a high-fat diet for 4 weeks to induce obesity, and subsequently, they were divided randomly into four groups: control, supplement, exercise-placebo, and exercise-supplement. The training groups performed aerobic exercise 5 days a week for 6 weeks (approximately 80-75% VOmax 2). The supplement groups received a solution of oak husk hydroalcoholic extract at a dose of 20 milligram per kilogram of body weight for 6 weeks. Blood samples were taken 48 h after the last training session, and the levels of IL-10, fibrinogen, IL-1ß, and nesfatin-1 were measured. Data were analyzed using one-way ANOVA and LSD post hoc tests. RESULTS: The results showed that six-week training and oak husk hydroalcoholic extract consumption significantly increased the levels of IL-10 and nesfatin-1 in experimental groups (P < 0.001). Also, the levels of fibrinogen and IL-1ß decreased significantly in training groups. Averages between group variations of all indicators were statistically significant, and they were more meaningfully pronounced in the exercise-supplement group than other groups (P ≤ 0.05). CONCLUSIONS: Considering the results of the present study, the use of moderate aerobic exercise and oak husk hydroalcoholic extract is recommended to reduce the risk of obesity; it may also have a positive effect on inflammatory factors.
Assuntos
Envelhecimento/patologia , Etanol/química , Inflamação/terapia , Obesidade/terapia , Condicionamento Físico Animal , Extratos Vegetais/uso terapêutico , Quercus/química , Água/química , Animais , Peso Corporal/efeitos dos fármacos , Fibrinogênio/metabolismo , Inflamação/complicações , Inflamação/tratamento farmacológico , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos Obesos , Nucleobindinas/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologiaRESUMO
That nesfatin-1 is a neuromodulatory peptide for the cardiovascular system is well documented. Several central receptors have been shown to mediate the cardiovascular effects of nesfatin-1. Immunohistochemistry and Western blot studies showed that nesfatin-1 activated the expression of the central cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX). In addition, microdialysis study showed that nesfatin-1 increased the release of total prostaglandins and leukotrienes from the hypothalamus. The present study investigated whether the central COX and LOX enzymes have a direct mediating role in the MAP and HR responses of nesfatin-1. Intracerebroventricularly administered nesfatin-1 produced dose-dependent pressor and phasic HR responses in normotensive conscious rats Sprague Dawley. Central pretreatment with a COX1/2 inhibitor, ibuprofen, completely blocked the nesfatin-1-induced responses. However, central pretreatment with a nonselective LOX inhibitor, nordihydroguaiaretic acid, partially attenuated the cardiovascular responses induced by nesfatin-1. The results suggest that centrally administered nesfatin-1 activates the central enzymes COX and LOX, which may be involved in the cardiovascular responses as a novel central mechanism for nesfatin-1.
Assuntos
Pressão Arterial/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Lipoxigenase/metabolismo , Nucleobindinas/administração & dosagem , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Sistema Cardiovascular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Relação Dose-Resposta a Droga , Hipotálamo/metabolismo , Ibuprofeno/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Nesfatin-1 and neuronostatin in the central nervous system participate in regulating stress responses. Glucocorticoid hormones affect the brain through glucocorticoid receptors (GR). We investigated in the rat the possibility of co-localizing nesfatin-1 and neuronostatin neurons in hypothalamic areas with GR. using immunohistochemistry. We counted nesfatin-1 and neuronostatin stained neurons. We counted GR positive nesfatin-1 neurons in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) and GR positive neuronostatin neurons in the periventricular nucleus (PeN). The percentage of nesfatin-1 neurons that expressed GR was 38.4% in female rats and 21.9% in male rats in the ARC, and 33.3% in female rats and 29.2% in male rats in the PVN. The percentage of neuronostatin neurons that expressed GR was 39.1% in female rats and 39.9% in male rats in the PeN. We found that a substantial portion of nesfatin-1 and neuronostatin neurons were stained for GR. We speculate that the pattern of GR might permit secretion of neuropeptides to be stimulated by peripheral glucocorticoid signals. Stress can suppress food intake, in part, through the GR in neurons that express nesfatin-1, which is a satiety molecule, and in neurons that express neuronostatin, which is an anorexigenic peptide.
Assuntos
Hipotálamo , Neurônios , Receptores de Glucocorticoides , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Hipotálamo/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Nucleobindinas , Fragmentos de Peptídeos , Ratos , SomatostatinaRESUMO
AIMS: The effective treatment of polycystic ovary syndrome (PCOS)-related hormonal disorders necessitates the development of novel treatment strategies. Resveratrol is found in certain food products, and is known to exhibit phytoestrogen properties. The present study was to assess whether resveratrol exhibits beneficial phytoestrogenic effects and associated hormonal modulation in a rat model of PCOS. MATERIALS AND METHODS: This model was established by administering oral letrozole to female Sprague-Dawley (SD) rats prior to randomizing them into control, model and resveratrol treatment groups (40, 80, or 160 mg/kg). Animals were treated for 30 days, after which time ovarian tissues were collected and evaluated via hematoxylin and eosin staining. In addition, serum levels of estradiol and adiponectin were assessed via ELISA, and ovarian expression of nesfatin-1 and aromatase was assessed through RT-PCR and western blotting. RESULTS: We found that resveratrol administration was associated with increased levels of plasma adiponectin and estradiol levels and restoration of normal ovarian morphology in PCOS model animals. In addition, this treatment was linked to the increased ovarian expression of nesfatin-1 and aromatase at the RNA and protein levels. CONCLUSIONS: Together things findings suggest that resveratrol may represent an effective tool for treating PCOS owing to its phytoestrogenic properties.
Assuntos
Ovário/efeitos dos fármacos , Fitoestrógenos/farmacologia , Síndrome do Ovário Policístico/patologia , Resveratrol/farmacologia , Adiponectina/metabolismo , Animais , Aromatase/efeitos dos fármacos , Aromatase/genética , Inibidores da Aromatase/toxicidade , Modelos Animais de Doenças , Estradiol/metabolismo , Feminino , Letrozol/toxicidade , Nucleobindinas/efeitos dos fármacos , Nucleobindinas/genética , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/metabolismo , Distribuição Aleatória , RatosRESUMO
The two peptides phoenixin and nesfatin-1 are colocalized in hypothalamic nuclei involved in the mediation of food intake and behavior. Phoenixin stimulates food intake and is anxiolytic, while nesfatin-1 is an anorexigenic peptide shown to increase anxiety and anhedonia. Interestingly, central activation of both peptides can be stimulated by restraint stress giving rise to a role in the mediation of stress. Thus, the aim of the study was to test whether also peripheral circulating levels of NUCB2/nesfatin-1 and phoenixin are altered by restraint stress. Male ad libitum fed Sprague Dawley rats equipped with a chronic intravenous catheter were subjected to restraint stress and plasma levels of NUCB2/nesfatin-1, phoenixin and cortisol were measured over a period of 240 min and compared to levels of freely moving rats. Peripheral cortisol levels were significantly increased in restrained rats at 30, 60, 120 and 240 min compared to controls (p < 0.05). In contrast, restraint stress decreased plasma phoenixin levels at 15 min compared to unstressed conditions (0.8-fold, p < 0.05). Circulating NUCB2/nesfatin-1 levels were increased only at 240 min in restrained rats compared to those in unstressed controls (1.3-fold, p < 0.05). In addition, circulating NUCB2/nesfatin-1 levels correlated positively with phoenixin levels (r = 0.378, p < 0.001), while neither phoenixin nor nesfatin-1 were associated with cortisol levels (r = 0.0275, and r=-0.143, p> 0.05). These data suggest that both peptides, NUCB2/nesfatin-1 and phoenixin, are affected by restraint stress, although less pronounced than circulating cortisol.
Assuntos
Nucleobindinas/metabolismo , Hormônios Peptídicos/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/sangue , Transtornos de Ansiedade/sangue , Encéfalo/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Hipotálamo/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Nucleobindinas/sangue , Nucleobindinas/fisiologia , Hormônios Peptídicos/sangue , Hormônios Peptídicos/fisiologia , Ratos , Ratos Sprague-Dawley , Restrição Física/psicologia , Estresse Psicológico/fisiopatologiaRESUMO
The vast majority of new neuropeptides feature unique biochemical properties as well as awide spectrum of physiological activity applied in numerous neuronal pathways, including hypothalamus and the limbic system. Special interest should be paid to nesfatin-1 - the relatively recently discovered and still intensively studied regulatory factor and a potential modulator of eating behaviors. New information about it now allows to consider this neuropeptide as a potentially important factor involved in the pathogenesis of many different mental disorders. The considered pharmacomodulation of nesfatinergic signaling may be potentially helpful in the future treatment of some neuropsychiatric and metabolic disorders including anorexia nervosa. Although the results of some basic and clinical tests seem to be promising, all possible applications of the aforementioned neuropeptides, together with their agonists and antagonists still remain in the area of speculation. The intensive search of selective modulators of their known receptors may facilitate the opening of a promising chapter in the eating disorders therapy. This paper provides a review of recent scientific reports regarding the hypothetical role of nesfatin-1 in the neuronal pathways related to pathophysiology of anorexia nervosa.
Assuntos
Regulação do Apetite/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Neuropeptídeos/metabolismo , Nucleobindinas/metabolismo , Anorexia Nervosa/metabolismo , Humanos , Hipotálamo/metabolismo , Imuno-Histoquímica , Fenômenos Fisiológicos do Sistema Nervoso , Neuroquímica , Neuropeptídeo Y/metabolismoRESUMO
Nesfatin-1 is a multifunctional neuropeptide having crucial autonomic roles. It is well known that nesfatin-1 collaborates with other central neuromodulatory systems, such as central corticotropin-releasing hormone, melanocortin, oxytocin, and cholinergic systems to show its autonomic effects. Central arachidonic acid cascade plays an important role to provide the homeostasis by exhibiting similar autonomic effects to nesfatin-1. Based on these similarities, the current study was designed to show the effects of intracerebroventricularly (ICV) injected nesfatin-1 on the hypothalamic arachidonic acid (AA) cascade. Immunochemistry and western blot approaches demonstrated that ICV administration of nesfatin-1 provokes an increase in the hypothalamic cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX) protein expression. Moreover, the microdialysis study demonstrated that centrally injected nesfatin-1 increased the posterior hypothalamic extracellular AA products. In conclusion, these findings report that while nesfatin-1 is generating its autonomic effects, it also might be using central prostaglandins and leukotrienes by activating central COX and LOX pathways.
Assuntos
Ácido Araquidônico/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Lipoxigenases/metabolismo , Nucleobindinas/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Injeções Intraventriculares , Masculino , Microdiálise , Nucleobindinas/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
Since its discovery in 2006 by Oh-I and colleagues, NUCB2/nesfatin-1 encoded by nucleobindin-2 (NUCB2) has drawn sustained attention as reflected in over 500 publications. Among those, more than half focused on the alterations of food intake, body weight and metabolism (glucose, fat) induced by nesfatin-1 and/or NUCB2/nesfatin-1. In the current review we discuss the existing literature focusing on NUCB2/nesfatin-1's influence on food intake, body weight and glucose as well as fat metabolism and highlight gaps in knowledge.
Assuntos
Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Nucleobindinas/metabolismo , Nucleobindinas/farmacologia , Animais , Gorduras/metabolismo , Glucose/metabolismo , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismoRESUMO
NUCB1 and NUCB2, two novel nucleobindins, have attracted extensive attention for their role in the appetite regulation in mammals. However, little is known about the appetite regulation of NUCB1 and NUCB2 in fish species. Therefore, we investigated the role of these peptides in the regulation of feeding in Schizothorax davidi (S. davidi). In this study, full-length cDNA sequences of nucb1 and nucb2A of S. davidi were obtained for the first time. Additionally, the tissue distribution and the effects of different energy status on nucb1 and nucb2A mRNAs abundance were assessed, showing that nucb1 and nucb2A are widely distributed in 18 detected tissues, with the highest expression in the cerebellum. The abundances of nucb1 and nucb2A increased in the hypothalamus at 1 h and 3 h post-feeding. Furthermore, fasting and re-feeding experiments showed that the expressions of nucb1 and nucb2A in hypothalamus significantly decreased after fasting for 7 days, and returned to the control level after re-feeding for 3 or 5 days. In conclusion, the present study suggests that both NUCB1 and NUCB2A are involved in the short-term and long-term appetite regulation, as an anorexigenic factor, in S. davidi. These results can provide a basis for further investigation into the appetite regulatory role of NUCB family in teleost.
Assuntos
Cyprinidae/genética , Proteínas de Peixes/genética , Privação de Alimentos , Hipotálamo/metabolismo , Nucleobindinas/genética , Animais , Feminino , Masculino , RNA Mensageiro/metabolismoRESUMO
Chronic hypernatremia activates the central osmoregulatory mechanisms and inhibits the function of the hypothalamic-pituitary-adrenal (HPA) axis. Noradrenaline (NE) release into the periventricular anteroventral third ventricle region (AV3V), the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN) from efferents of the caudal ventrolateral (cVLM) and dorsomedial (cDMM) medulla has been shown to be essential for the hypernatremia-evoked responses and for the HPA response to acute restraint. Notably, the medullary NE cell groups highly coexpress prolactin-releasing peptide (PrRP) and nesfatin-1/NUCB2 (nesfatin), therefore, we assumed they contributed to the reactions to chronic hypernatremia. To investigate this, we compared two models: homozygous Brattleboro rats with hereditary diabetes insipidus (DI) and Wistar rats subjected to chronic high salt solution (HS) intake. HS rats had higher plasma osmolality than DI rats. PrRP and nesfatin mRNA levels were higher in both models, in both medullary regions compared to controls. Elevated basal tyrosine hydroxylase (TH) expression and impaired restraint-induced TH, PrRP and nesfatin expression elevations in the cVLM were, however, detected only in HS, but not in DI rats. Simultaneously, only HS rats exhibited classical signs of chronic stress and severely blunted hormonal reactions to acute restraint. Data suggest that HPA axis responsiveness to restraint depends on the type of hypernatremia, and on NE capacity in the cVLM. Additionally, NE and PrRP signalization primarily of medullary origin is increased in the SON, PVN and AV3V in HS rats. This suggests a cooperative action in the adaptation responses and designates the AV3V as a new site for PrRP's action in hypernatremia.
Assuntos
Adaptação Fisiológica , Hipernatremia/fisiopatologia , Hipotálamo/fisiopatologia , Bulbo/fisiopatologia , Nucleobindinas/fisiologia , Hormônio Liberador de Prolactina/fisiologia , Animais , Masculino , Nucleobindinas/análise , Hormônio Liberador de Prolactina/análise , Ratos Brattleboro , Ratos Wistar , Estresse Psicológico/metabolismo , Tirosina 3-Mono-Oxigenase/análiseRESUMO
Nesfatin-1 is a peptide derived from nucleobindin-2 and involved in the regulation of food intake and hyperglycemia. Nesfatin-1 is a recently described anorexigenic peptide, which may be involved in weight loss, malnutrition, and the regulation of appetite. Nesfatin-1 has an effect on the regulation of glucose homeostasis as well as that of food intake. The aim of this article is to bring a different perspective to the readers on the effects of nesfatin-1 on food intake and hyperglycemia. The central injection of nesfatin-1 may produce anorexigenic effects. The circulating level of nesfatin-1 is thought to be regulated by nutritional status. Long-term changes in body weight can affect nesfatin-1 levels. In overweight and obese individuals, nesfatin-1 levels may increase. Nesfatin-1 is synthesized in the hypothalamic appetite control regions. Nesfatin-1 levels may decrease in individuals with diabetes but may increase in those with impaired glucose tolerance. Nesfatin-1 may have a reducing effect on glucose levels. In addition, an increase in glucose levels may lead to an increase in the release of nesfatin-1 from pancreatic cells. Injection of nesfatin-1 can prevent hepatic glucose formation and stimulate glucose uptake. Reduction of hypothalamic nesfatin-1 levels increases hepatic glucose flow and decreases glucose uptake from peripheral tissues. In the light of all this information, nesfatin-1 may be considered to be an important regulator in the metabolic process. Nesfatin-1 appears to be able to contribute to the treatment of obesity and diabetes because of its anorexigenic and antihyperglycemic effects. Key teaching pointsNesfatin-1 is a anorexigenic peptide.Nesfatin-1 is derived from Nucleobindin-2.Nucleobindin-2 mRNA is produced in different areas of the brain.Nesfatin-1 is an inhibitory factor on appetite and a regulator of energy balance that reduces the increase in body weight.
Assuntos
Depressores do Apetite/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Hiperglicemia/metabolismo , Nucleobindinas/metabolismo , Animais , Apetite/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Hipotálamo/metabolismo , Nucleobindinas/biossíntese , Estado Nutricional/efeitos dos fármacosRESUMO
Nucleobindin-1 is an EF-hand calcium-binding protein with a distinctive profile, predominantly localized to the Golgi in insect and wide-ranging vertebrate cell types, alike. Its putative involvements in intracellular calcium (Ca2+) homeostasis have never been phenotypically characterized in any model organism. We have analyzed an adult-viable mutant that completely disrupts the G protein α-subunit binding and activating (GBA) motif of Drosophila Nucleobindin-1 (dmNUCB1). Such disruption does not manifest any obvious fitness-related, morphological/developmental, or behavioral abnormalities. A single copy of this mutation or the knockdown of dmnucb1 in restricted sets of cells variously rescues pleiotropic mutant phenotypes arising from impaired inositol 1,4,5-trisphosphate receptor (IP3R) activity (in turn depleting cytoplasmic Ca2+ levels across diverse tissue types). Additionally, altered dmNUCB1 expression or function considerably reverses lifespan and mobility improvements effected by IP3R mutants, in a Drosophila model of amyotrophic lateral sclerosis. Homology modeling-based analyses further predict a high degree of conformational conservation in Drosophila, of biochemically validated structural determinants in the GBA motif that specify in vertebrates, the unconventional Ca2+-regulated interaction of NUCB1 with Gαi subunits. The broad implications of our findings are hypothetically discussed, regarding potential roles for NUCB1 in GBA-mediated, Golgi-associated Ca2+ signaling, in health and disease.
Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Cálcio/metabolismo , Proteínas de Drosophila/fisiologia , Receptores de Inositol 1,4,5-Trifosfato/genética , Nucleobindinas/fisiologia , Alelos , Motivos de Aminoácidos , Animais , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Genes Letais , Pleiotropia Genética , Complexo de Golgi/metabolismo , Homeostase , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Mutação , Nucleobindinas/química , Nucleobindinas/genética , Nucleobindinas/metabolismo , Domínios Proteicos , Homologia Estrutural de ProteínaRESUMO
The exact mechanisms of polycystic ovary syndrome (PCOS) are unknown and there is no effective cure for the disease. The aim of this study was to evaluate the alterations in serum oestradiol and adiponectin levels and in the expression of some important genes in the uterine and ovarian tissues of PCOS rats. The therapeutic effect of quercetin on PCOS was also assessed. Rats were divided into five groups: control, ethanol, quercetin (Q), PCOS and PCOS+Q. After 30 days of oral treatments, the rats' ovaries and uteri were removed and nesfatin-1, aromatase and adipoR1 expressions were quantified with real-time polymerase chain reaction. Serum adiponectin and oestradiol levels were evaluated using enzyme-linked immunosorbent assay technique. The results of this study showed that expression of nesfatin-1 and adipoR1 genes and adiponectin serum levels decreased in the PCOS rats, but aromatase expression and oestradiol level increased. Treatment with quercetin increased the adiponectin level and expression of adipoR1 and nesfatin-1 and decreased both the expression of aromatase and the oestradiol level. Quercetin improved PCOS by phytoestrogenic effects and mimicking oestrogen's function. Quercetin also affects important factors in both the uterus and ovary and could improve the obesity and the diabetic and infertility symptoms of PCOS.
Assuntos
Desidroepiandrosterona , Ovário/efeitos dos fármacos , Fitoestrógenos/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Quercetina/farmacologia , Útero/efeitos dos fármacos , Adiponectina/sangue , Animais , Aromatase/metabolismo , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Nucleobindinas/metabolismo , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Ratos Sprague-Dawley , Receptores de Adiponectina/metabolismo , Útero/metabolismo , Útero/fisiopatologiaRESUMO
There is growing evidence that obstructive sleep apnoea (OSA) influences the hypothalamic-pituitary-gonadal axis (HPG axis) in men. The aim of the study was to assess the association of nesfatin-1 with HPG axis disturbances in OSA. This is a prospective study with consecutive enrolment. It comprises 72 newly diagnosed OSA patients ((AHI: apnoea-hypopnea index) 18 subjects: 5 ≤ AHI < 15; 24: 15 ≤ AHI < 30; 30: AHI ≥ 30) and a control group composed of 19 patients (AHI < 5). All patients underwent polysomnography and fasting blood collection for nesfatin-1, testosterone, luteinising hormone (LH), high-sensitivity C-reactive protein (hsCRP), aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine and glucose. Groups had similar levels of LH, nesfatin-1 and testosterone (p = 0.87; p = 0.24; p = 0.08). Nesfatin-1 was not correlated to LH (p = 0.71), testosterone (p = 0.38), AHI (p = 0.34) or the oxygen desaturation index (ODI) (p = 0.69) either in the whole group, or in sub-groups. The study did not reveal any association between the HPG axis and nesfatin-1 in OSA adult males. It is possible that nesfatin-1 is not a mediator of HPG axis disturbances in adult patients with OSA.
Assuntos
Gônadas/metabolismo , Hipotálamo/metabolismo , Nucleobindinas/metabolismo , Hipófise/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Idoso , Glicemia/análise , Jejum , Humanos , Masculino , Pessoa de Meia-Idade , Nucleobindinas/sangue , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/sangueRESUMO
Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.