Publications about Nesfatin 1

Publication

Nesfatin-1 promotes VSMC migration and neointimal hyperplasia by upregulating matrix metalloproteinases and downregulating PPARγ.

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

October/1/2018

Abstract

The dedifferentiation, proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the progression of hypertension, atherosclerosis and intimal hyperplasia. Nesfatin-1 is a potential modulator in cardiovascular functions. However, the role of nesfatin-1 in VSMC biology has not been explored. The present study was designed to determine the regulatory role of nesfatin-1 in VSMC proliferation, migration and intimal hyperplasia after vascular injury. Herein, we demonstrated that nesfatin-1 promoted VSMC phenotype switch from a contractile to a synthetic state, stimulated VSMC proliferation and migration in vitro. At the molecular level, nesfatin-1 upregulated the protein and mRNA levels, as well as the promoter activities of matrix metalloproteinase 2 (MMP-2) and MMP-9, but downregulated peroxisome proliferator-activated receptor γ (PPARγ) levels and promoter activity in VSMCs. Blockade of MMP-2/9 or activation of PPARγ prevented the nesfatin-1-induced VSMC proliferation and migration. In vivo, knockdown of nesfatin-1 ameliorated neointima formation following rat carotid injury. Taken together, our results indicated that nesfatin-1 stimulated VSMC proliferation, migration and neointimal hyperplasia by elevating MMP2/MMP-9 levels and inhibiting PPARγ gene expression.

Authors

Ji-Ru Zhang; Qing-Bo Lu; Wu-Bing Feng; Hui-Ping Wang; Zi-Han Tang; Han Cheng+4 authors

Publication

Plasma nesfatin-1 and glucoregulatory hormone responses to two different anaerobic exercise sessions.

Journal: European Journal of Applied Physiology

December/9/2010

Abstract

Nesfatin-1 is a recently discovered anorectic protein derived from posttranslational processing of the nucleobindin 2 (NUCB2) gene. It is expressed in adipose tissue and is also found in plasma. Nesfatin-1 expression is significantly affected by nutritional status and its actions may be involved in the inhibition of the orexigenic effect of ghrelin. Although the effects of physical exercise on several anorectic and orexigenic hormones have been reported, no studies have investigated its effects upon circulating concentrations of nesfatin-1. We investigated the effects of acute strenuous interval exercise and circuit exercise on nesfatin and other hormones affected by metabolic stress. Fourteen provincial and national level young male-kickboxing volunteers participated [age 20.71 ± 2.6 years, height 176.6 ± 2.8 cm, body weight 67.2 ± 3.3 kg, and body mass index (BMI) 21.56 ± 1.42 kg/m(2)]. After an overnight fast, responses to a running-based anaerobic sprint test (RAST; 7 sets of 6 × 35 m every 10 s with 1 min rest in between sets) and a non-combat kickboxing session (NCKB; 7 sets of 6 techniques, 20 s per technique with 1 min rest in between sets) were determined. Venous blood samples were collected before, immediately after, and 45 as well as 95 min following the exercises. Plasma GH, insulin, glucose and lactate concentrations significantly increased immediately following the RAST and NCKB protocols, however, plasma nesfatin-1 concentrations were not significantly altered. Higher plasma cortisol and glucose concentrations occurred in response to the RAST compared with the NCKB protocols. Although the exercise protocols elicited metabolic stress that significantly altered circulating glucoregulatory hormones, plasma glucose and lactate, there was no significant change in plasma nesfatin-1. A lack of nesfatin-1 response to the exercise protocols may be partially due to the fasting condition.

Authors

Abbass Ghanbari-Niaki; Robert R Kraemer; Raheleh Soltani

Publication

Nesfatin-1 stimulates glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide secretion from STC-1 cells in vitro.

Journal: Biochemical and Biophysical Research Communications

August/3/2015

Abstract

Nesfatin-1 is an 82 amino acid peptide encoded in a secreted precursor, nucleobindin 2. It is an anorexigenic and insulinotropic peptide found abundantly in the hypothalamus, pancreas and gastric oxyntic mucosa. NUCB2 mRNA expression is 10 fold higher in the gastric mucosa than in brain, suggesting gastrointestinal tract as a main source of nesfatin-1. Meal responsive insulin secretion is regulated by incretins glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). Since both nesfatin-1 and incretins modulate insulin secretion, we hypothesized that nesfatin-1 is present in the enteroendocrine cells, and that it regulates incretin secretion. RT-PCR analysis found NUCB2 mRNA expression, and immunofluorescence microscopy determined nesfatin-1 immunoreactivity in STC-1, an enteroendocrine cell line. NUCB2/nesfatin-1 is co-localized with GLP-1 and GIP in mouse small intestinal cells. Static incubation of STC-1 cells with nesfatin-1 upregulated preproglucagon (GLP-1 precursor) mRNA (0.01, 0.1, 1 and 10 nM) and GLP-1 secretion (0.1, 1 and 10 nM). Nesfatin-1 also enhanced GIP mRNA (0.1, 1 and 10 nM) and GIP secretion (1 and 10 nM). Together, our data support the hypothesis that nesfatin-1 is present in enteroendocrine cells and that it stimulates incretin secretion. Future studies should aim for nesfatin-1 and incretin interactions in vivo.

Authors

Naresh Ramesh; Sima Mortazavi; Suraj Unniappan

Publication

Nesfatin-1; implication in stress and stress-associated anxiety and depression.

Journal: Current Pharmaceutical Design

July/21/2014

Abstract

Nesfatin-1, derived from an 82-amino-acid peptide precursor protein nucleobindin-2 (NUCB2), is a highly conserved peptide across mammalian species. Initial functional and neuroanatomical studies on NUCB2/nesfatin-1 in the central nervous system have supported a role for NUCB2/nesfatin-1 as a novel satiety molecule. In recent years, however, it has become apparent that this neuropeptide is involved in various other processes, one of which is the stress response. Stress-associated activation of NUCB2/nesfatin-1 neurons, together with nesfatin-1's central actions in the brain, is indicative of its significance in the stress adaptation response. Interestingly, increasing body of evidence implicates also NUCB2/nesfatin-1 in various forms of stress-associated psychopathologies, such as anxiety and depression. In this review, we will outline evidence that has significantly broadened our understanding of the biological significance of NUCB2/nesfatin-1 far beyond to be only a hypothalamic peptide with potent anorexigenic actions. NUCB2/nesfatin-1 neurons in the brain seem to emerge as novel, integral regulators of the stress adaptation response.

Authors

T L Emmerzaal; T Kozicz

Publication

Nesfatin-1 correlates with hypertension in overweight or obese Han Chinese population.

Journal: Clinical and Experimental Hypertension

September/22/2015

Abstract

We investigated blood nesfatin-1 levels in hypertension patients. We found that fasting plasma nesfatin-1 levels were significantly higher in hypertension patients than in control groups, especially in overweight/obese hypertension patients (4.5 ± 2.1 versus 3.3 ± 1.1 ng/ml, p < 0.01). Body mass index, systolic blood pressure and diastolic blood pressure were indeed positively correlated with fasting plasma nesfatin-1 levels (r = 0.234, p < 0.05; r = 0.304, p < 0.01; r = 0.251, p < 0.05; r = 0.461, p < 0.01; respectively). Logistic regression analysis revealed that the plasma level of nesfatin-1 could be independent of risk prediction over standard measures (OR = 1.547, 95% CI: 1.153-6.273, p = 0.026). Nesfatin-1 has the incremental contribution to hypertension risk prediction (IDI: 0.014, p = 0.018; NRI: 0.050, p = 0.043). The plasma nesfatin-1 level in hypertension patients with microalbuminuria are significantly higher than those without microalbuminuria patients (6.4 ± 2.1 ng/ml versus 3.9 ± 1.8 ng/ml, p < 0.01). Nesfatin-1 might play an important role in obesity hypertension, and its increase could be a risk factor for obesity-associated hypertension.

Authors

Yanyan Zhao; Xiaojun Ma; Qingzhu Wang; Yingni Zhou; Yuanyuan Zhang; Lina Wu+5 authors

Publication

Paraventricular NUCB2/Nesfatin-1 Supports Oxytocin and Vasopressin Neurons to Control Feeding Behavior and Fluid Balance in Male Mice.

Journal: Endocrinology

June/4/2017

Abstract

Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.

Authors

Masanori Nakata; Darambazar Gantulga; Putra Santoso; Boyang Zhang; Chiaki Masuda; Masatomo Mori+2 authors

Publication

Impact of intracerebroventricular obestatin on plasma acyl ghrelin, des-acyl ghrelin and nesfatin-1 levels, and on gastric emptying in rats.

Journal: Molecular Medicine Reports

September/9/2012

Abstract

Obestatin, which is a putative 23-amino-acid peptide, is derived from the C-terminal part of the mammalian preproghrelin gene. Nesfatin-1 mRNA is co-expressed with ghrelin in gastric endocrine X/A-like cells; therefore, nesfatin-1 may also interact with preproghrelin gene products in the stomach. In this study, we investigated the impact of obestatin on the plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, and on the gastric emptying of a solid nutrient meal 2 h after an intracerebroventricular (ICV) injection in conscious, fasted rats. The rats were implanted with ICV catheters. Plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, expected to be co-expressed with obestatin, were measured, whereas the human/rat corticotropin-releasing factor (h/rCRF) was applied as an inhibitor of gastric emptying. The ICV administration of obestatin (0.1, 0.3 and 1.0 nmol/rat) did not modify the plasma acyl ghrelin and des-acyl ghrelin levels, the acyl ghrelin/des-acyl ghrelin ratio and nesfatin-1 concentrations. The ICV acute administration of obestatin had no influence on the 2-h rate of gastric emptying of a solid nutrient meal, but the ICV h/rCRF injection delayed it. The weight of food ingested 1 h before ICV injection significantly, but negatively correlated with the gastric emptying of a solid nutrient meal. Our study indicates that the ICV injection of obestatin does not change the 2-h rate of gastric emptying of a solid nutrient meal and the relatively weak interrelationships between ghrelin gene products and nesfatin-1. However, the weight of the ingested food negatively affects the gastric emptying of a solid nutrient meal in conscious, fasted rats.

Authors

Chih-Yen Chen; Wei-Jei Lee; Keong Chong; Shou-Dong Lee; You-Di Liao

Publication

Emerging roles of NUCB2/nesfatin-1 in the metabolic control of reproduction.

Journal: Current Pharmaceutical Design

July/21/2014

Abstract

Nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as a feeding-suppressing neuropeptide, acting at central (mainly, hypothalamic) levels in a leptin-independent manner. However, recent experimental evidence strongly suggests that, rather than being a simple anorectic hypothalamic signal, nesfatin-1 operates at different tissues as an integral regulator of energy homeostasis and closely related neuroendocrine functions. On the latter, growing, albeit as yet fragmentary, evidence has pointed out recently that NUCB2/ nesfatin-1 is involved in the regulation of different aspects of reproductive maturation and function, by acting probably at different levels of the hypothalamic-pituitary-gonadal (HPG) axis. As documented by rodent studies, the reproductive facet of nesfatin-1 likely includes (i) a permissive role in (female) pubertal maturation, (ii) stimulatory effects on the gonadotropic axis, whose magnitude, in terms of LH responses, varies depending on the maturational stage and probably the sex and species, and (iii) direct expression and actions in the gonads. These features, together with the proven expression of NUCB2/nesfatin-1 in tissues with essential roles in the metabolic control of reproduction, such as the hypothalamus, adipose and pancreas, support a putative role of nesfatin-1 as neurohormonal signal linking body metabolic status, puberty and fertility. Curiously enough, although its reproductive dimension seems to be conserved in non-mammalian vertebrates, recent studies in goldfish have surfaced predominant inhibitory actions of nesfatin-1 at different levels of the HPG axis in fish. These findings illustrate our as yet limited understanding of this aspect of nesfatin-1 physiology, whose relevance in the joint control of metabolism and reproduction in health and disease warrants further investigation.

Authors

David García-Galiano; Manuel Tena-Sempere

Publication

Lipopolysaccharide increases gastric and circulating NUCB2/nesfatin-1 concentrations in rats.

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Journal: Peptides

January/11/2012

Abstract

Bacterial lipopolysaccharide (LPS) is an established animal model to study the innate immune response to Gram-negative bacteria mimicking symptoms of infection including reduction of food intake. LPS decreases acyl ghrelin associated with decreased concentrations of circulating ghrelin-O-acyltransferase (GOAT) likely contributing to the anorexigenic effect. We also recently described the prominent expression of the novel anorexigenic hormone, nucleobindin2 (NUCB2)/nesfatin-1 in gastric X/A-like cells co-localized with ghrelin in different pools of vesicles. To investigate whether LPS would affect gastric and circulating NUCB2/nesfatin-1 concentration, ad libitum fed rats were equipped with an intravenous (iv) catheter. LPS was injected intraperitoneally (ip, 100μg/kg) and blood was withdrawn before and at 2, 5, 7 and 24h post injection and processed for NUCB2/nesfatin-1 radioimmunoassay. Gastric corpus was collected to measure NUCB2 mRNA expression by RT-qPCR and NUCB2/nesfatin-1 protein concentration by Western blot. Injection of LPS increased plasma NUCB2/nesfatin-1 concentrations by 43%, 78% and 62% compared to vehicle at 2h, 5h and 7h post injection respectively (p<0.05) and returned to baseline at 24h. The plasma NUCB2/nesfatin-1 increase at 2h was associated with increased corpus NUCB2 mRNA expression (p<0.01), whereas NUCB2 mRNA was not detectable in white blood cells. Likewise, gastric NUCB2 protein concentration was increased by 62% after LPS compared to vehicle (p<0.01). These data show that gastric NUCB2 production and release are increased in response to LPS. These changes are opposite to those of ghrelin in response to LPS supporting a differential gastric regulation of NUCB2/nesfatin-1 and ghrelin expression derived from the same cell by immune challenge.

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Authors

Andreas Stengel; Miriam Goebel-Stengel; Janusz Jawien; Peter Kobelt; Yvette Taché; Nils W G Lambrecht

Publication

The protective effect of nesfatin-1 against renal ischemia-reperfusion injury in rats.

Journal: Renal Failure

June/5/2016

Abstract

BACKGROUND

The pathogenetic mechanisms underlying ischemia-reperfusion (I/R) injury involve oxidative stress, inflammation and apoptosis. Nesfatin-1, a novel peptide, has been reported to possess antioxidant, anti-inflammatory and anti-apoptic properties. The study was to examine the potential protective effects of nesfatin-1 on renal I/R injury.

METHODS

I/R model was induced by placing a clamp across left renal artery for 45 min followed by 24 h reperfusion, along with a contralateral nephrectom. Twenty-four rats divided into three groups: sham-operated group, vehicle-treated I/R and nesfatin-1-treated I/R. Nesfatin-1 was intraperitoneally injected 30 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. Marker of oxidative stress and cells in kidney were also evaluated.

RESULTS

The animals with nesfatin-1 significantly improved renal functional and histologic lesions induced by I/R injury. The malondialdehyde (MDA) level decreased, whereas superoxide dismutase (SOD) and catalase (CAT) activities were significantly increased. Moreover, nesfatin-1-treated rats had a markedly decrease in apoptotic tubular cells, as well as a decrease in caspase-3 activity and an increase in the bcl-2/Bax ratio.

CONCLUSIONS

This is the first evidence that nesfatin-1 treatment ameliorates acute renal I/R injury by suppressing oxidative stress and cell apoptosis. Therefore, it is promising as a potential therapeutic agent for renal IR injury.

Authors

Guanjun Jiang; Min Wang; Lei Wang; Hui Chen; Zhiyuan Chen; Jia Guo+2 authors

Publication

Evaluating the Levels of Nesfatin-1 and Ghrelin Hormones in Patients with Moderate and Severe Major Depressive Disorders.

Journal: Psychiatry Investigation

November/12/2018

Abstract

OBJECTIVE

The goal of this study was to evaluate the importance of nesfatin-1, acylated and des-acylated ghrelin, which are known as energy regulatory hormones, in patients with moderate and severe major depression disorders (MDD).

METHODS

Thirty patients with a moderate degree of MDD and, 30 with a severe degree of MDD were used as participants in this study. Thirty subjects without depression were enrolled as a control group. The Hamilton Depression Rating Scale was used to classify the patients with MDD. Blood samples were taken after overnight fasting. The plasma nesfatin-1, acylated ghrelin and des-acylated ghrelin levels were measured using a commercially available enzyme-linked immunosorbent assay kit.

RESULTS

The nesfatin-1, the acylated ghrelin and the des-acylated ghrelin levels were found to be significantly higher in severe MDD (3.92±0.4 ng/mL; 88.56±4.1 pg/mL; 962.76±67 pg/mL) as compared to moderate MDD (2.91±0.5 ng/mL; 77.63±4.19 pg/mL; 631.16±35 pg/mL), or the control (1.01±0.3 ng/mL; 58.60±9.00 pg/mL; 543.13±62 pg/mL), respectively.

CONCLUSIONS

Although nesfatin-1 and ghrelin are known as adversely affecting the hormones involving the regulation of appetite and food intake, they all increase in depressive patients and are even associated with the severity of the disease. In clinical medicine, the evaluation of the role of nesfatin-1 and ghrelin in endocrine and neu-roendocrine regulation of major metabolic functions is an important key mechanism in solving numerous diseases associated with endocrine and neuroendocrine disturbance. Increased levels of nesfatin-1 and ghrelin may also be important criteria in describing the prognoses of the patients and the effectiveness of the treatments.

Authors

Sermin Algul; Oguz Ozcelik

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Citations(5)Authors(2)

Publication

Nesfatin-1-Like Peptide Encoded in Nucleobindin-1 in Goldfish is a Novel Anorexigen Modulated by Sex Steroids, Macronutrients and Daily Rhythm.

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Journal: Scientific Reports

February/19/2017

Abstract

Nesfatin-1 is an 82 amino acid anorexigen encoded in a secreted precursor nucleobindin-2 (NUCB2). NUCB2 was named so due to its high sequence similarity with nucleobindin-1 (NUCB1). It was recently reported that NUCB1 encodes an insulinotropic nesfatin-1-like peptide (NLP) in mice. Here, we aimed to characterize NLP in fish. RT- qPCR showed NUCB1 expression in both central and peripheral tissues. Western blot analysis and/or fluorescence immunohistochemistry determined NUCB1/NLP in the brain, pituitary, testis, ovary and gut of goldfish. NUCB1 mRNA expression in goldfish pituitary and gut displayed a daily rhythmic pattern of expression. Pituitary NUCB1 mRNA expression was downregulated by estradiol, while testosterone upregulated its expression in female goldfish brain. High carbohydrate and fat suppressed NUCB1 mRNA expression in the brain and gut. Intraperitoneal injection of synthetic rat NLP and goldfish NLP at 10 and 100 ng/g body weight doses caused potent inhibition of food intake in goldfish. NLP injection also downregulated the expression of mRNAs encoding orexigens, preproghrelin and orexin-A, and upregulated anorexigen cocaine and amphetamine regulated transcript mRNA in goldfish brain. Collectively, these results provide the first set of results supporting the anorectic action of NLP, and the regulation of tissue specific expression of goldfish NUCB1.

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Authors

Lakshminarasimhan Sundarrajan; Ayelén Melisa Blanco; Juan Ignacio Bertucci; Naresh Ramesh; Luis Fabián Canosa; Suraj Unniappan

Publication

Nesfatin-1 protects dopaminergic neurons against MPP+/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway.

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Journal: Scientific Reports

February/19/2017

Abstract

Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson's disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro. We show that nesfatin-1 attenuates the loss of nigral dopaminergic neurons in the 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. In addition, nesfatin-1 antagonized 1-methyl-4-phenylpyridillium ion (MPP+)-induced toxicity by restoring mitochondrial function, inhibiting cytochrome C release and preventing caspase-3 activation in MPP+-treated MES23.5 dopaminergic cells. These neuroprotective effects could be abolished by selective inhibition of C-Raf and the extracellular signal-regulated protein kinase 1/2 (ERK1/2). Our data suggest that C-Raf-ERK1/2, which is involved in an anti-apoptotic pathway, is responsible for the neuroprotective effects of nesfatin-1 in the context of MPTP-induced toxicity. These results imply that nesfatin-1 might have therapeutic potential for PD.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247731/bin/srep40961-f7.jpg

Authors

Xiao-Li Shen; Ning Song; Xi-Xun Du; Yong Li; Jun-Xia Xie; Hong Jiang

Publication

Quercetin Alleviates LPS-Induced Depression-Like Behavior in Rats via Regulating BDNF-Related Imbalance of Copine 6 and TREM1/2 in the Hippocampus and PFC.

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Journal: Frontiers in Pharmacology

February/3/2020

Abstract

Quercetin is a polyphenol with multiple biological activities, and results of our preliminary study showed that it could shorten the immobility time of mice in the forced swimming test and tail suspending test. The aim of this study was to investigate its effects on the behavioral performance of lipopolysaccharide (LPS)-challenged rats and explore the potential mechanism. The results showed that intragastrical administration of quercetin (40 mg/kg) could improve the bodyweight gain of LPS-challenged rats, increase the saccharin preference index in the saccharin preference test and the novel arm preference index in the Y-maze, and decrease the immobility time in the FST. However, it showed no significant effect on the performance of LPS-challenged rats in the Morris water maze and the plasma concentrations of nesfatin-1, C-reactive protein (CRP), and IL-6. Results of western blot showed that the expression levels of BDNF, Copine 6, p-TrkB, and the triggering receptors expressed on myeloid cells (TREM) 1 were decreased in both the hippocampus and the prefrontal cortex (PFC) of LPS-challenged rats, while the expression of TREM2 was increased. The protein expression of synapsin-1 was decreased in the hippocampus without significant changes in the PFC. These imbalance protein expressions could be balanced by treatment with quercetin. The results suggested that quercetin could alleviate LPS-induced depression-like behaviors and impairment of learning and memory in rats, the mechanism of which might be involved with regulating the BDNF-related imbalance expression of Copine 6 and TREM1/2 in the hippocampus and the PFC.

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Authors

Fang Ke; Hua-Rong Li; Xing-Xing Chen; Xin-Ran Gao; Ling-Ling Huang; An-Qi Du+3 authors

Publication

The Relationship between Nesfatin-1 Levels and SYNTAX Score in Patients with Non-ST Segment Elevation Myocardial Infarction.

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Journal: Acta Cardiologica Sinica

November/13/2018

Abstract

UNASSIGNED

Nesfatin-1 is a novel anorectic neuropeptide with potent metabolic regulatory effects. It regulates blood pressure, heart rate, cardiomyocyte metabolism and permeability. SYNTAX score, which is an angiographic scoring system, defines the grade and complexity of coronary artery disease (CAD). We aimed to evaluate the relationship between nesfatin-1 level and severity of CAD according to the SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI).

UNASSIGNED

A total of 109 subjects were enrolled into the study, of whom 80 underwent coronary angiography (CA) with the diagnosis of NSTEMI and 29 had normal coronary arteries detected in CA. NSTEMI patients were divided into 2 groups: low SYNTAX score (< 32) (45 patients) and high SYNTAX score (≥ 32) (35 patients).

UNASSIGNED

The NSTEMI patients with a high SYNTAX score (score ≥ 32) had a lower serum nesfatin-1 level (62 pg/ml; 39-98) compared to the NSTEMI patients with a low SYNTAX score (score < 32) (138 pg/ml; 65-286) and the control group (392 pg/ml; 178-1320). There was also a negative correlation between serum nesfatin-1 level and SYNTAX score (r = -0.594, p < 0.001). A lower serum level of nesfatin-1 (odds ratio = 0.116; 95% confidence interval: 0.138- 0.094; p < 0.001) was an independent predictor for high SYNTAX score in the NSTEMI patients after multiple linear regression analysis.

UNASSIGNED

Serum nesfatin-1 level was lower in the high SYNTAX group than in the low SYNTAX group in patients with NSTEMI. Nesfatin-1could have a role in the pathogenesis of atherosclerotic burden in patients with NSTEMI.

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Authors

Mevlüt Serdar Kuyumcu; Aliye Kuyumcu; Çağrı Yayla; Mustafa Bilal Özbay; Sefa Ünal; Burak Açar+3 authors

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Citations(5)Authors(9)

Publication

Tissue-specific expression of ghrelinergic and NUCB2/nesfatin-1 systems in goldfish (Carassius auratus) is modulated by macronutrient composition of diets.

Journal: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology

November/10/2016

Abstract

The macronutrient composition of diets is a very important factor in the regulation of body weight and metabolism. Several lines of research in mammals have shown that macronutrients differentially regulate metabolic hormones, including ghrelin and nesfatin-1 that have opposing effects on energy balance. This study aimed to determine whether macronutrients modulate the expression of ghrelin and the nucleobindin-2 (NUCB2) encoded nesfatin-1 in goldfish (Carassius auratus). Fish were fed once daily on control, high-carbohydrate, high-protein, high-fat and very high-fat diets for 7 (short-term) or 28 (long-term) days. The expression of preproghrelin, ghrelin O-acyl transferase (goat), growth hormone secretagogue receptor 1 (ghs-r1) and nucb2/nesfatin-1 mRNAs was quantified in the hypothalamus, pituitary, gut and liver. Short-term feeding with fat-enriched diets significantly increased nucb2 mRNA levels in hypothalamus and liver, preproghrelin, goat and ghs-r1 expression in pituitary, and ghs-r1 expression in gut. Fish fed on a high-protein diet exhibited a significant reduction in preproghrelin and ghs-r1 mRNAs in the liver. After long-term feeding, fish fed on high-carbohydrate and very high-fat diets had significantly increased preproghrelin, goat and ghs-r1 expression in pituitary. Feeding on a high-carbohydrate diet also upregulated goat and ghs-r1 transcripts in gut, while feeding on a high-fat diet elicited the same effect only for ghs-r1 in liver. Nucb2 expression increased in pituitary, while it decreased in gut after long-term feeding of a high-protein diet. Collectively, these results show for the first time in fish that macronutrients differentially regulate the expression of ghrelinergic and NUCB2/nesfatin-1 systems in central and peripheral tissues of goldfish.

Authors

Ayelén M Blanco; Juan I Bertucci; María J Delgado; Ana I Valenciano; Suraj Unniappan

Publication

Irisin interaction with adipose tissue secretions by exercise training and flaxseed oil supplement.

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Journal: Lipids in Health and Disease

January/18/2019

Abstract

<AbstractText>Previous studies have shown that physical training and natural diet able to change the expression and concentration of peptides and proteins. Myokines and adipokines play an important role in metabolism and metabolic syndrome. Therefore, the purpose of the present study was to investigate the effect of high-intensity interval training (HIIT) and supplementation of flaxseed oil on plasma irisin, nesfatin-1 and resistin in male rats.</AbstractText><AbstractText>Forty adult male rats were randomly divided into four groups (ten in each group) including Control-Saline (CS), Training-Saline (TS), Control-FlaxOil supplement (CO), and Training-FlaxOil supplement (TO). The training groups performed for 10 weeks and 5 sessions each week, interval training with 90-95% VO2max on rodent treadmill, and supplement groups received flaxseed oil (300 mg / kg). Five days after the last training session, rats were sacrificed. Blood samples were taken from the heart and plasma was evaluated.</AbstractText><AbstractText>Exercise Training significantly increased plasma levels of irisin (P = 0.019), nesfatin-1 (P = 0.01), and decreased resistin (P = 0.01). Flaxseed oil significantly reduced plasma resistin levels (P = 0.02). Plasma irisin levels in the supplementation group were higher than all groups (P = 0.041).</AbstractText><AbstractText>There was a significant positive correlation between plasma levels of irisin with nesfatin-1 and negative correlation with resistin. HIIT program with flaxseed oil as a modality can create a metabolic crosstalk between skeletal muscle and adipose tissues and have health benefits.</AbstractText>

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Authors

Hossein Shirvani; Saleh Rahmati-Ahmadabad

Publication

Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

Journal: Neuropeptides

March/3/2016

Abstract

Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic pathways, which has potential clinical applications.

Authors

Ewa Rojczyk; Artur Pałasz; Ryszard Wiaderkiewicz

Publication

Nesfatin-1 improves oxidative skin injury in normoglycemic or hyperglycemic rats.

Journal: Peptides

December/12/2016

Abstract

Hyperglycemia is one of the major causes of suppressed angiogenesis and impaired wound healing leading to chronic wounds. Nesfatin-1 a novel peptide was reported to have antioxidant and anti-apoptotic properties. This study is aimed to investigate the potential healing-promoting effects of nesfatin-1 in non-diabetic or diabetic rats with surgical wounds. In male Sprague-Dawley rats, hyperglycemia was induced by intraperitoneal (ip) injection of streptozotocin (55 mg/kg). Under anesthesia, dorsum skin tissues of normoglycemic (n=16) and hyperglycemic rats were excised (2 × 2 cm, full-thickness), while control rats (n=16) had neither hyperglycemia nor wounds. Half of the rats in each group were treated ip with saline, while the others were treated with nesfatin-1 (2 μg/kg/day) for 3 days until they were decapitated. Plasma interleukin-1-beta (IL-1β), transforming growth factor-beta (TGF-β-1), IL-6 levels, and dermal tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) and caspase-3 activity were measured. For histological examination, paraffin sections were stained with hematoxylin-eosin or Masson's trichrome and immunohistochemistry for vascular endothelial growth factor (VEGF) was applied. ANOVA and Student's t-tests were used for statistical analysis. Compared to control rats, skin MPO activity, MDA and caspase-3 levels were increased similarly in saline-treated normo- and hyperglycemic rats. Nesfatin-1 depressed MDA, caspase-3, MPO activity and IL-1β with concomitant elevations in dermal GSH and plasma TGF-β-1 levels. Histopathological examination revealed regeneration of epidermis, regular arrangement of collagen fibers in the dermis and a decrease in VEGF immunoreactivity in the epidermal keratinocytes of nesfatin-1-treated groups. Nesfatin-1 improved surgical wound healing in both normo- and hyperglycemic rats via the suppression of neutrophil recruitment, apoptosis and VEGF activation.

Authors

Ali Solmaz; Elif Bahadır; Osman B Gülçiçek; Hakan Yiğitbaş; Atilla Çelik; Ayça Karagöz+3 authors

Publication

Nesfatin-1 and Vitamin D levels may be associated with systolic and diastolic blood pressure values and hearth rate in polycystic ovary syndrome.

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Journal: Bosnian Journal of Basic Medical Sciences

June/6/2016

Abstract

Obesity, insulin resistance (IR), inflammation, and hyperandrogenism may lead to polycystic ovary syndrome (PCOS) and hypertension. Nesfatin-1 (N1) may be related to IR, obesity, and hypertension. Furthermore, a vitamin D (VD) deficiency is associated with hypertension and PCOS. We aimed to investigate N1 and VD levels in PCOS that have an effect on systolic and diastolic blood pressure (BP) and heart rate (HR).This study included 54 patients with PCOS and 48 age-body mass index (BMI)-matched healthy controls. PCOS was diagnosed according to clinical practice guidelines. Ferriman-Gallwey scores (FGS) were calculated, while N1, VD, and other hormonal and biochemical parameters were measured for all subjects. Systolic and diastolic BP was measured as well. HR was calculated using an electrocardiogram.The levels of N1 (p < 0.001), high-sensitivity C-reactive protein (hs-CRP) (p = 0.036), homeostasis model assessment as an index of insulin resistance (HOMA-IR) (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) BP and HR (p < 0.001) in the PCOS group were significantly higher than in the control group. However, the VD levels of the PCOS group were lower than the control group (p = 0.004). N1 had a strong positive correlation with BMI, HOMA-IR, hs-CRP, luteinizing hormone, systolic and diastolic BP, and HR. VD levels were negatively correlated with HOMA-IR and luteinizing hormone.Elevated N1 and decreased VD levels may be related to the presence of high-normal BP or hypertension in PCOS subjects. N1 level may be associated with an increased BP due to its relation to inflammation and IR.

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Authors

Figen Kir Sahin; Serap Baydur Sahin; Ulku Mete Ural; Medine Cumhur Cure; Senol Senturk; Yesim Bayoglu Tekin+4 authors

Publication

Cord blood nesfatin-1 in large for gestational age pregnancies.

Journal: Cytokine

July/22/2013

Abstract

OBJECTIVE

To investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic β-cells and implicated in glucose metabolism and insulin resistance), as well as insulin, in large (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms.

METHODS

Cord blood nesfatin-1 and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from non-diabetic mothers) and 20 AGA singleton full-term infants as well as their mothers.

RESULTS

Cord blood nesfatin-1 concentrations were significantly lower in LGA compared to AGA neonates (b=-0.206, SE 0.07, p=0.005). However, cord blood nesfatin-1 concentrations were elevated in infants born from mothers with gestational diabetes mellitus (GDM), compared to those born from non-diabetic mothers, after controlling for group (b=0.190, SE 0.10, p=0.05). Finally, cord blood nesfatin-1 concentrations were lower in cases of vaginal delivery (b=0.11, SE 0.05, p=0.042). Insulin levels were significantly elevated, as customized centiles increased (b=0.004, SE=0.002, p=0.016). No significant correlation was found between insulin and nesfatin-1 in maternal and umbilical cord levels.

CONCLUSIONS

In this study nesfatin-1 levels are decreased in LGA compared to AGA fetuses. Fetal nesfatin-1 concentrations are higher in cases of GDM and cord blood nesfatin-1 concentrations are lower in cases of vaginal delivery.

Authors

Theodora Boutsikou; Despina D Briana; Maria Boutsikou; George Kafalidis; Despoina Piatopoulou; Stavroula Baka+3 authors

Publication

Progesterone and 17β-estradiol regulate expression of nesfatin-1/NUCB2 in mouse pituitary gland.

Journal: Peptides

September/4/2016

Abstract

Nesfatin-1 was first shown to be involved in the control of appetite and energy metabolism in the hypothalamus. Many recent reports have shown nesfatin-1 expression in various tissues including the pituitary gland, but its expression and regulation mechanisms in the pituitary gland are unclear. Therefore, first, we investigated the mRNA and protein expression of nesfatin-1 in the pituitary using qRT-PCR and Western blotting, respectively. Expression of NUCB2 mRNA and nesfatin-1 protein was higher in the pituitary gland than in other organs, and nesfatin-1 protein was localized in many cells in the anterior pituitary gland. Next, we investigated whether NUCB2 mRNA expression in the pituitary gland was regulated by sex steroid hormones secreted by the ovary. Mice were ovariectomized and injected with progesterone (P4) and 17β-estradiol (E2). The expression of NUCB2 in the pituitary gland was dramatically decreased after ovariectomy and increased with injection of P4 and E2, respectively. The in vitro experiment to elucidate the direct effect of P4 and E2 on NUCB2 mRNA expression showed NUCB2 mRNA expression was significantly increased with E2 and decreased with P4 alone and P4 plus E2 in cultured pituitary tissue. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the mouse pituitary and was regulated by P4 and E2. These data suggest that reproductive-endocrine regulation through hypothalamus-pituitary-ovary axis may contribute to nesfatin-1/NUCB2 expression in the pituitary gland.

Authors

Yiwa Chung; Jinhee Kim; Eunji Im; Heejeong Kim; Hyunwon Yang

Publication

Regulation of NucB2/Nesfatin-1 throughout rat pregnancy.

Journal: Physiology and Behavior

February/18/2015

Abstract

Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic role during pregnancy and fetal development and its energy balance mediating role should be studied in various physiological and pathological conditions throughout gestation.

Authors

María F Garcés; Natalia E Poveda; Elizabeth Sanchez; Ángel Y Sánchez; Susana B Bravo; María J Vázquez+3 authors

Publication

Serum nesfatin-1 levels are decreased in pregnant women newly diagnosed with gestational diabetes.

Journal: Archives of endocrinology and metabolism

November/21/2017

Abstract

OBJECTIVE

To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters.

METHODS

Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed.

RESULTS

Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30).

CONCLUSIONS

Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.

Authors

Esra Nur Ademoglu; Suheyla Gorar; Muge Keskin; Ayse Carlioglu; Rifki Ucler; Husamettin Erdamar+2 authors

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