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Phoenixin-14 (PNX) is a neuropeptide that has been shown to prevent oxidative damage and stimulates insulin secretion. We investigated the effects of PNX on pancreatic injury induced by streptozotocin (STZ), and nicotinamide (NAD). Male Sprague-Dawley rats, in control (C) and diabetic (STZ) groups, were treated with either saline, or PNX (0.45 nmol/kg, or 45 nmol/kg) daily for 3 days 1 week after STZ injection. Fasting blood glucose (FBG) and gastric emptying rate (GER) were measured. Tissue and blood samples were collected. PNX treatments prevented pancreatic damage and β cell loss. Increased luminol and lucigenin levels in the pancreas, ileum and liver tissues of STZ groups were alleviated by PNX treatment in pancreatic and ileal tissues. PNX0.45 decreased FBG without any change in insulin blood level and pancreatic mRNA. GER increased in all diabetic rats while PNX0.45 delayed GER only in the C group. PNX diminishes pancreatic damage and lowers FBG by reducing oxidative load.

Gestational diabetes mellitus (GDM) is a common disease in pregnant women, imposing risks on both mother and fetus. Dysregulated nesfatin-1 has been observed in women with GDM, but the specific role of nesfatin-1 underlying the pathological process of GDM is unclear. The main objective of this study is to investigate the role and the molecular mechanism of nesfatin-1 in GDM. HTR-8/SVneo cells were treated with high glucose (HG)/high lipid (HL) to mimic the injured trophoblast of GDM in vitro. Cell viability, cytotoxicity and apoptosis were measured using CCK-8, LDH and TUNEL assays, respectively. The levels of inflammatory cytokines and antioxidant factors were detected using their commercial kits. ATP level and cytochrome c were determined with corresponding detecting kits. Quantitative real-time PCR and Western blot were performed to detect the expression of corresponding genes. The results showed that nesfatin-1 was downregulated upon HG/HL stimulation. Nesfatin-1 treatment greatly alleviated HG/HL-induced cell viability loss, cytotoxicity, inflammatory response, oxidative stress, and apoptosis in HTR-8/SVneo cells. In addition, nesfatin-1 promoted ATP generation, reduced the leakage of cytochrome c from mitochondria to cytoplasm, and upregulated mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), alleviating mitochondrial dysfunction. Furthermore, nesfatin-1 inhibited p38 MAPK signaling. p79350, an agonist of p38 MAPK signaling, remarkably hindered the protective role of nesfatin-1 in HG/HL-induced HTR-8/SVneo cells. In conclusion, nesfatin-1 exerted a protective effect on GDM model in vitro, by regulating p38 MAPK signaling pathway, providing novel insights of treating GDM.

Objective: The pathogenesis of endometriosis has not been clearly explained. Inflammatory factors of ectopic implantation and the growth of ectopic endometrial cells have been subjects of major interest. The number of studies evaluating salusin-α and nesfatin-1 markers in patients with endometriosis is limited. No studies have evaluated the levels of anti-inflammatory markers for adropin and netrin-1 in patients with endometriosis. This study investigates how some important inflammatory regulatory markers in the inflammatory process affect the pathogenesis of endometriosis and determines whether any relationship exists between serum levels of these parameters and endometriosis and insulin resistance. Materials and methods: This prospective study included 73 patients with endometriosis diagnosed histopathologically after laparoscopic surgery and 75 healthy controls. Serum adropin, salusin-α, netrin-1, and nesfatin-1 levels and homeostatic model assessment of insulin resistance (HOMA-IR) values of the participants were measured. Results: The endometriosis group had significantly lower nesfatin-1 levels than the control group (3.0±0.53 vs 9.5±0.94, p=0.005). Between the patient and control groups, there was no difference regarding serum adropin, salusin-α, and netrin-1 levels (p=0.36, p=0.34, p=0.75, respectively). Nesfatin-1 had a significant positive correlation with adropin, salusin-α, and netrin-1 (r=0.563, p

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3-4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother's milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3-4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

IntroductionGlucagon-like peptide-1 (GLP-1) anorexigenic and anti-obesogenic effects are centrally mediated. Data on animals emphasize the importance of neuronal GLP-1 receptor (GLP-1R) for feeding suppression, although it is unclear whether astrocytes participate in the transduction of anorectic GLP-1R-dependent signals. In humans, the brain circuitry underlying these effects remains insufficiently investigated. GLP-1R neuroanatomic localization in human hypothalamus, a brain region with a pivotal role in energy homeostasis regulation, is essential in order to improve our understanding of GLP-1 signaling pathways and central metabolic functions. The present study aimed to explore GLP-1R protein expression in human hypothalamus and its correlation with body mass index (BMI).MethodsSections of hypothalamus from 28 autopsy cases, 11 with normal weight (BMI < 25 Kg/m2) and 17 with non-normal weight (BMI ≥ 25 Kg/m2), were examined using immunohistochemistry and double immunofluorescence labeling.ResultsProminent GLP-1R immunoexpression was detected in neurons of several hypothalamic nuclei, including paraventricular, supraoptic, and infundibular nuclei, lateral hypothalamic area (LH), and basal forebrain nuclei. Interestingly, in LH, GLP-1R protein expression was significantly decreased in individuals with BMI ≥ 25 Kg/m2, compared with normal weight counterparts (p=0.03). Furthermore, GLP-1R was moderately and negatively correlated (τb=-0.347, p=0.024) with BMI levels only in the LH. GLP-1R extensively colocalized with the anorexigenic and anti-obesogenic neuropeptide nucleobindin-2/nesfatin-1, but not with the astrocytic marker glial fibrillary acidic protein (GFAP).ConclusionThese data suggest a potential role for GLP-1R in the regulation of energy balance in human hypothalamus, possibly through interactions with nesfatin-1. In LH, an appetite- and reward-related brain region, reduced GLP-1R immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior. GLP-1R colocalization with nesfatin-1 in the basal forebrain, a cognition-related brain area, might give impetus towards elucidating additional central actions of GLP-1R.

Diabetes, mobile phone use, and obesity have increased simultaneously in recent years. The radiofrequency radiation (RFR) emitted from mobile phones is largely absorbed in the heads of users. With 5 G, which has started to be used in some countries without the necessary precautions being taken, the amount of RFR to which living things are exposed will increase. In this study, the changes in energy homeostasis and redox balance caused by 5 G (3.5 GHz, GSM-modulated) were explored. The effects of RFR on the brains of diabetic and healthy rats were investigated and histopathological analysis was performed. Twenty-eight Wistar albino rats weighing 200-250 g were divided into 4 groups as sham, RFR, diabetes, and RFR+diabetes groups (n = 7). The rats in each group were kept in a plexiglass carousel for 2 h a day for 30 days. While the rats in the experimental groups were exposed to RFR for 2 h a day, the rats in the sham group were kept under the same experimental conditions but with the radiofrequency generator turned off. At the end of the experiment, brain tissues were collected from euthanized rats. Total antioxidant (TAS), total oxidant (TOS), hydrogen peroxide (H2O2), ghrelin, nesfatin-1, and irisin levels were determined. In addition, histopathological analyses of the brain tissues were performed. The specific absorption rate in the gray matter of the brain was calculated as 323 mW/kg and 195 mW/kg for 1 g and 10 g averaging, respectively. After RFR exposure among diabetic and healthy rats, decreased TAS levels and increased TOS and H2O2 levels were observed in brain tissues. RFR caused increases in ghrelin and irisin and a decrease in nesfatin-1 in the brain. It was also observed that RFR increased the number of degenerated neurons in the hippocampus. Our results indicate that 3.5 GHz RFR causes changes in the energy metabolism and appetite of both healthy and diabetic rats. Thus, 5 G may not be innocent in terms of its biological effects, especially in the presence of diabetes., Van Yuzuncu Yil University Scientific Research Foundation (BAP, Turkey); [TYD-2021-9598], This work was supported by Van Yuzuncu Yil University Scientific Research Foundation (BAP, Turkey, grant number: TYD-2021-9598) . The authors would like to thank Dr. Mustafa Cakir and Yusuf Emir Bektas ? for their valuable contribution.

Nutrition is a body function exhibited to provide the metabolic needs of the organism. The regulation of feeding behavior is provided by homeostatic mechanisms. Food consumption of individuals is time-dependently coordinated by the brain throughout the approximately 24-hour circadian cycle. The biological clocks in the body set the daily intervals in which food consumption can occur in the circadian rhythm. These time zones are usually in the active period phase. The biological clocks that provide circadian control of food intake are a light-entrained master clock in the suprachiasmatic nucleus of the hypothalamus and numerous secondary oscillators in the brain and other tissues of the body. Nesfatin-1 is a hormone derived from the precursor protein of nucleobindin 2 and has strong effects on appetite. The anorexigenic effect of Nesfatin-1 is more pronounced, especially in the dark period of the day. This raises the question of whether the hormone in question has a circadian rhythm. In our review, the findings obtained from the studies on the subject are discussed cross-sectionally, and the possible relationship between the regulation of feeding behavior and the effects of nesfatin-1 with the circadian rhythm is evaluated., Beslenme, organizmanın metabolik ihtiyaçlarını karşılamak için sergilenen bir vücut fonksiyonudur. Beslenme davranışının regülasyonu homeostatik mekanizmalar tarafından sağlanmaktadır. Bireylerin gıda tüketimi, yaklaşık 24 saatlik sirkadiyen döngü boyunca beyin tarafından zamana bağlı olarak koordine edilir. Vücuttaki biyolojik saatler gıda tüketiminin sirkadiyen ritimde meydana gelebileceği günlük aralıkları ayarlamaktadır. Bu zaman dilimleri genellikle aktif periyot evresinde yer almaktadır. Besin alımının sirkadiyen kontrolünü sağlayan biyolojik saatler, hipotalamusun suprakiazmatik nükleusunda ışıkla sürüklenen (entrain) bir ana saat ile beyinde ve vücudun diğer dokularında yer alan çok sayıdaki sekonder osilatörlerdir. Nesfatin-1, nükleobindin 2 öncü proteininden türetilen ve iştah üzerinde güçlü etkiler gösteren bir hormondur. Nesfatin-1’in anoreksijenik etkisi özellikle günün karanlık periyodunda daha belirgindir. Bu durum söz konusu hormonun sirkadiyen ritme sahip olup olmadığı sorusunu akıllara getirmektedir. Derlememizde konuyla ilgili çalışmalardan elde edilen bulgular kesitsel olarak ele alınarak, nesfatin-1’in beslenme davranışının regülasyonu ile etkilerinin sirkadiyen ritimle muhtemel ilişkisi değerlendirilmektedir.

Background/Aim: Preoperative fasting, fluid restriction and stress trigger many hormonal responses, one of which is the newly described Nefsatin-1. It has important effects on energy metabolism and stress. In this study, we aimed to examine the relationship between stress, fasting, fluid restriction, and Nesfatin-1. Methods: A total of 100 ASA I-II adult patients between 18 and 60 years of age with no psychiatric, cardiovascular, or metabolic disorders, who were operated under general anesthesia for various reasons at Fırat University Hospital between June and November 2013 were included in this randomized prospective case-control study. Patients were categorized into fluid restriction (Group 1) and no-fluid restriction (Group 2) groups. These groups were further sub-categorized as those receiving (Groups 1A and 2A) and not receiving pre-medication (Group 1B and Group 2B). State Trait Anxiety Inventory was applied to all patients by an independent member of the research team before the surgical procedure. Also, blood samples were obtained 6-8 hours, 1 hour, and just before the induction to measure insulin, glucose, epinephrine, norepinephrine, cortisol, and Nesfatin-1 levels. Results: In both groups, the test score for pre-operative anxiety was 44. While there were no differences in serum insulin levels between the study groups (P>0.05), serum glucose and epinephrine levels were higher in Group 1A than in other groups (P

Background Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug. Methods Studies were carried out on adult, male Sprague–Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression. Results Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged. Conclusions Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.

Nesfatin-1 and nesfatin-1-like peptide (Nlp) are derived from precursors nucleobindin-2 and -1, two calcium and DNA binding proteins, respectively. Both peptides exhibit hormone-like actions in mammals and fish. These functions include insulinotropic effects of nesfatin-1 and Nlp seen in mice and their growth hormone suppressive actions reported in goldfish. We hypothesized that nesfatin-1 and Nlp are insulin stimulatory (in adipose tissue) and modulate growth hormone and insulin-like growth factors and glucose transporters in goldfish. To test this, goldfish were intraperitoneally injected with either nesfatin-1 or Nlp (50 ng/g BW) or saline alone (control) and sampled at one-hour post-injection (in vivo study). In a separate study, tissue samples were collected and were incubated with either nesfatin-1 or Nlp for one or six hours (in vitro study). Transcript (mRNA) abundance data from the adipose tissue suggest that both nesfatin-1 and Nlp significantly upregulate the abundance of preproinsulin, insulin receptors, and pcsk1 and pcsk2 mRNAs. Meanwhile, the abundance of preproglucagon mRNA in the adipose tissue was significantly downregulated in both in vivo and in vitro studies. These results agree with the insulinotropic and glucagonostatic roles for nesfatin-1 and Nlp reported in rodents. The transcript abundance of growth regulators (igf1, igf2a, and ghra) and glucose transporters (slc2a2 and slc5a1) were upregulated in the muscle, while an opposite effect on these mRNAs was found in the liver of goldfish following nesfatin-1 and Nlp administration. Our results suggest that both nesfatin-1 and Nlp have tissue-specific regulatory roles on growth and glucoregulatory elements in the liver and muscle of goldfish. This agrees with our previous studies that showed a suppressive action of nesfatin-1 on growth hormone in goldfish liver. The results presented here provide strong supportive/confirmatory evidence for tissue-specific insulinotropic and gluco- and growth-regulatory actions of nesfatin-1 and Nlp in goldfish.

Nesfatin-1 is a newly found food and water intake regulatory neuropeptide. Because it can regulate nutrition and thirst, nesfatin-1 may also have the potential to affect levels of blood electrolytes and metabolites. The current study was intended to resolve the acute influence of intracerebroventricularly injected nesfatin-1 on the levels of some blood electrolytes and metabolites in rats. The experiments were conducted on Sprague Dawley male rats. Nesfatin-1 (200 pmol) or saline (5 μL) was given the rats intracerebroventricularly. Central nesfatin-1 treatment caused increases in the concentrations of blood glucose, lactate, hematocrit, and hemoglobin without changing the blood pH, creatine, Na, K, Ca, Cl, and HCO3 levels. In conclusion, our findings show that the central nesfatin-1 could affect the concentrations of blood glucose, lactate, hematocrit, and hemoglobin without altering the blood electrolytes. This could be interpreted as the secondary effect of nesfatin-1 as a consequence of centrally injected nesfatin-1-evoked activation of sympathetic nerves.

Background and objective: Nesfatin-1 is a newly described peptide, derived from nucleobindin2. Nesfatin-1 suppresses food intake and it is involved in regulating insulin secretion. The aim of this study was to compare serum levels of Nesfatin-1 in patients having type 2 diabetes and non-diabetic subjects. Methods: This cross-sectional study included 90 participants; 64 patients with type 2 diabetes mellitus (32 males and 32 females) and 26 control subjects (13 males and 13 female). Body mass index, fasting serum level of glucose, fasting serum level of insulin, and glycated hemoglobin were estimated. Homeostasis model assessment of insulin resistance was calculated. Nesfatin-1 level was measured using enzyme-linked immune-sorbent assay kit. The data was analyzed using Graphpad prism 7.04 for windows. Results: Type 2 diabetes patients aged from 33-78 years and the control group aged from 32-75 years. Nesfatin-1 level in the diabetic group was significantly lower than controls. The median interquartile range (IQR) of Nesfatin-1 was 0.765 (0.4-1.173) in diabetes and 1.02 (0.775-1.458) in controls. The diabetes group has significantly higher homeostasis model assessment of insulin resistance compared with non-diabetics. Serum Nesfatin-1 was correlated negatively with body mass index, fasting serum glucose, fasting serum insulin, glycatedhemoglobin, and homeostasis assessment of insulin resistance. Conclusion: Serum Nesfatin-1 level is negatively correlated with fasting serum glucose, fasting serum insulin, and glycated hemoglobin. This association supports the role of Nesfatin-1 in increased insulin resistance in patients with type 2 diabetes.

Objective The prevalence of childhood obesity is increasing and leads to co-morbidities such as hypertension. However, it is still not clear why some obese individuals are hypertensive and others not. Nesfatin-1 is a recently discovered anorexigenic peptide which also has effects on blood pressure (BP). Our aim was to evaluate the relationship between obesity-related hypertension and Nesfatin-1. Methods This cross-sectional study comprised 87 obese children. The patients were divided into two groups; hypertensive (n=30) and normotensive (n=57) obese. The American Academy of Pediatrics guidelines were used to diagnose hypertension. Blood samples were collected after 12 hours of fasting to investigate Nesfatin-1 concentrations. We also evaluated serum trace elements in addition to the routine blood tests. Results Body mass index (BMI), weight and serum Nesfatin-1 concentrations were higher in the hypertensive group (p=0.002, p=0.001, and p=0.007, respectively). There was no difference between serum zinc levels, but Copper (Cu) levels were significantly lower in the hypertensive group (p=0.248, p=0.007, respectively). There were positive correlations between BP and BMI and weight Z-scores and a negative correlation with Cu. The optimal cut-off value of Nesfatin-1 to predict hypertension was found to be >1.8 ng/mL, with a specificity of 71.9% and a sensitivity of 96.7% [area under the curve=0.703, 95% confidence interval (CI): 0.577-0.809; p=0.002]. In multiple logistic regression analysis Nesfatin-1 [Odds ratio (OR)=1.103, 95% CI: 1.039-1.171; p=0.001], Cu (OR=0.947, 95% CI: 0.915-0.979; p=0.001) and BMI for age Z-score (OR=56.277, 95% CI: 5.791-546.907; p=0.001) still remained significant predictors of hypertension. Conclusion Nesfatin-1 levels are higher and are an independent predictor of hypertension in obese subjects.

Osteoarthritis (OA) is a chronic degenerative joint disease, related to the overexpression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), inflammation, and chondrocyte apoptosis. Nesfatin-1 is an adipokine, which plays an important role in the development of OA, especially in obese people. In the present study, cartilage degradation and apoptosis observed in OA patients was evaluated. Furthermore, the anti-inflammatory and anti-apoptotic effects of nesfatin-1, and its underlying in vitro and in vivo mechanisms were investigated. The results showed that nesfatin-1 increased significantly the expression of collagen type II alpha 1 chain (Col2a1), and reduced the expression of MMPs, ADAMTS5, cyclooxygenase (COX)-2, caspase-3, nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), interleukin (IL)-6, and chondrocyte apoptosis rate, which may be induced by IL-1β in rat chondrocytes. Furthermore, nesfatin-1 treatment prevented cartilage degeneration in the rat OA model. It was found that nesfatin-1 suppressed the IL-1β-induced activation of NF-κB, the mitogen-activated protein kinase (MAPK), and the Bax/Bcl-2 signal pathway in chondrocytes. These results suggest that in vivo nesfatin-1 could play a protective role in the development of OA and can be potentially used for its treatment.

Despite continuous efforts to address classical risk factors for atherosclerosis, the battle to control the disease is far from over and atherosclerosis is still a major factor in all-cause mortality. To investigate the relations between early diagnosis and severity of coronary atherosclerosis we examined vaspin and nesfatin-1 levels, and the presence of fragmented QRS (fQRS) in admission electrocardiograms.We divided 168 patients into asymptomatic control (18%),50% coronary artery stenosis (28%),50% stenosis (31%) and myocardial infarction (MI) (23%) groups. Patients were also evaluated in anatomically significant (50%stenosis ​+ ​MI) and non-significant atherosclerosis (control+50%stenosis) groups. Vaspin and nesfatin-1 levels were measured using ELISA methods.Vaspin in MI and50% stenosis groups was lower than in other groups (p ​ ​0.001). Nesfatin-1 in MI and50% stenosis groups was lower only than in50%stenosis group (p0.007). The presence of fQRS was higher in MI and50% stenosis groups than other groups (p ​ ​0.001). In the anatomically significant atherosclerosis group, vaspin, nesfatin-1 and left ventricular ejection fraction (LVEF) values were lower while Gensini score and the presence of fQRS were higher (for all p ​ ​0.001). Lower vaspin levels and fQRS were related to in-hospital mortality (p ​ ​0.001 and p ​= ​0.02,respectively). Logistic regression analysis showed that male gender, diabetes mellitus, smoking, family history, lower LVEF, lower vaspin and fQRS were defined as independent risk factors for anatomically significant atherosclerosis (p ​= ​0.001).Our results indicate that low vaspin and fQRS were found to be novel independent risk factors for anatomically significant atherosclerosis and were predictors of mortality.

Background and objectives Nesfatin-1 as a potent anorexigenic peptide is secreted by pancreatic β cells. Conflicting data are available about its level among diabetic patients. Our study aimed to assess nesfatin-1 levels in newly diagnosed drug-naïve diabetic and pre-diabetic patients and its association with cardio-metabolic risk and insulin resistance (IR). This case-control study included drug-naive patients with DMT2 (group 1, n = 30) and pre-diabetes (group 2, n = 30) in addition to healthy subjects (group 3, n = 28). Anthropometric and routine biochemical assessments were performed. Serum nesfatin-1and plasma insulin levels were assessed by ELISA methods. Homeostatic model for assessment of IR (HOMA-IR) was calculated. Results Serum nesfatin-1 was significantly lower in diabetic and pre-diabetic compared to healthy subjects (3.89 ± 1.1 ng/dl and 7.47 ± 1.22 ng/dl versus 15.39 ± 3.53 respectively, p < 0.001). Also diabetic patients had statistically significant lower nesfatin-1 levels than pre-diabetic patients (p < 0.001) Roc curve analysis identified cut-off values of ≤ 9 ng/dl and ≤ 5.5 ng/dl with an AUC of 0.94 and 0.97, sensitivity of 96.7 and 100%, and specificity of 93.3% and 96.7% for diagnosis of pre-diabetes and diabetes respectively. Using bivariate analysis, nesfatin-1 was negatively correlated with glycemic parameters (fasting and 2 h postprandial blood sugar, HBA1c), IR parameters (fasting insulin and HOMA-IR) and atherogenic lipid profile (triglyceride, cholesterol, and LDL-c); and positively correlated to HDL-c in both diabetic and pre-diabetic but not in healthy. Conclusion Nesfatin-1 is an excellent predictor for pre-diabetes and DMT2. It is associated with favorable glucose and lipid metabolism probably via insulin signaling pathway.

Background This study aimed to explore the effect of nesfatin-1 on cobalt chloride (CoCl2)-induced hypoxic injury in cardiomyocyte H9c2 cells. Methods H9c2 cardiomyocytes were induced by different concentrations of CoCl2 to mimic the hypoxia condition. Cell viability was detected by MTT assay. Cell apoptosis was detected by TUNEL staining and flow cytometry. ROS production was detected using the fluorescence probe DCFH-DA. The mitochondrial membrane potential (MMP) was detected using the TMRE method. The levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were detected using the commercial kits. The protein levels of MAPK signaling members (p-JNK1/2, p-ERK1/2, and p-p38) and Notch1 signaling members (Notch1, Hes 1, and Jagged 1) were detected by Western blot. Results CoCl2 significantly promoted cell apoptosis, increased LDH leakage, MDA concentration, and decreased cell viability, SOD activity, GSH production, and CAT activity. CoCl2-induced hypoxic injury in H9c2 cells was partially restored by nesfatin-1 treatment. Moreover, nesfatin-1 treatment attenuated CoCl2-induced increase in ROS production and mitochondrial dysfunction, decreased mitochondrial membrane potential, Bax/Bcl-2 imbalance, as well as c-caspase-9 and c-caspase-3 levels. Moreover, nesfatin-1 treatment inhibited the activation of MAPK and Notch1 signaling pathways. Conclusions Nesfatin-1 could effectively protect H9c2 cells against CoCl2-induced hypoxic injury by blocking MAPK and Notch1 signaling pathways, suggesting that nesfatin-1 might be a promising therapeutic agent for hypoxic cardiac injury.

Objective Delta-like 1 (DLK1) and nesfatin-1 are adipokines that have been shown to affect glucose metabolism. We aimed to search serum DLK1 and nesfatin-1 concentrations at 24-28 weeks of pregnancy in women newly defined with gestational diabetes mellitus (GDM) and investigate the relationship of these adipokines with various metabolic parameters. Methods Serum levels of DLK1 and nesfatin-1 were evaluated in 44 women with GDM, and in 40 healthy pregnant women by enzyme-linked immunosorbent assay (ELISA) kits. While performing oral glucose tolerance test (OGTT) for GDM diagnosis at 24-28 weeks of pregnancy, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles, glycosylated hemoglobin (HbA1c) were also measured. Results Maternal serum DLK1 and nesfatin-1 concentrations were found lower in pregnant women with GDM compared with healthy pregnant women (418.4±282.6 vs. 586.7±303 ng/L, p=0.002; 12.2±7.6 vs. 26.7±16.4 ng/ml, p

Objective Delta-like 1 (DLK1) is known to inhibit adipocyte differentiation and nesfatin-1 is a neuropeptide that plays a role in the regulation of nutrition and metabolism. We aimed to assess both the levels of DLK1 and nesfatin-1 in polycystic ovary syndrome (PCOS) and determine the association of DLK1 and nesfatin-1 with metabolic parameters. Materials and methods Forty-four patients with PCOS and 40 healthy women as the control group were included in this study. Venous blood samples of the participants were collected, and hormonal, metabolic parameters, DLK1 and nesfatin-1 blood levels were determined. Anthropometric parameters were also determined. For a double comparison, the Mann-Whitney U test was used for non-parametric numerical data, and Student's t-test was used for parametric numerical data. Bivariate correlations were investigated using Spearman's correlation analysis. The diagnostic performance of the parameters was evaluated using receiver operating characteristic curve analysis. Results The findings showed that DLK1 and nesfatin-1 levels were lower among the PCOS group, and the differences in these values were found to be statistically significant. A significant negative correlation was found between DLK1 levels and body mass index (BMI), waist/hip ratio, visceral adiposity index (VAI), fasting serum insulin (FSI), homeostasis model of assessment-insulin resistance (HOMA-IR) and triglyceride levels. A significant negative correlation was found between nesfatin-1 levels and BMI, VAI, FSI, HOMA-IR and triglyceride. Conclusion The findings showed that DLK1 and nesfatin-1 levels were lower in PCOS. Based on this study, DLK1 may be culpable for metabolic disorders in PCOS and can be a novel marker for PCOS in the future.

Introduction: Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemia-reperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia. Methods: The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 µg/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining. Results: NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P

Objective: to investigate the diagnostic value of nesfatin-1 in cases of intestinal ischemia and ischemia/reperfusion. Study Design: An experimental study. Place and Duration of Study: the Experimental Animals Laboratory of Bezmialem University, in June 2018. Methodology: twenty-one healthy male Sprague Dawley rats were randomly divided into three groups of 7 rats each. In group 1: 1-hour intestinal ischemia followed by 5-hour reperfusion was performed. In group 2: rats were subjected to 6-hour intestinal ischemia. In group 3: rats underwent laparotomy and closure without performing any further procedure. Changes in leukocyte count, amylase, blood sugar, LDH, SGOT, CRP, and nesfatin-1 levels were determined. For histopathological examination, a small intestinal sample was taken and preserved in 10% formaldehyde. Results: nesfatin-1 value in group 2 was significantly higher than that in group 1 and group 3 (p=0.005, and p, NA

WOS: 000496445800010 PubMed ID: 31280388 AimIn Parkinson's disease (PD), oxidative stress plays a substantial role in degeneration of dopaminergic neurons at the substantia nigra. Recent reports describe nesfatin-1 and glucagon-like peptide-1 (GLP-1) as molecules with neuroprotective property that relieve oxidative stress. In this study, we aimed to determine the blood levels of nesfatin-1, GLP-1 and oxidative stress status in patients with PD.Material and methodForty patients with PD, followed-up at the Department of Neurology of Mugla Sitki Kocman University Training and Research Hospital, were enrolled, as well as 40 age- and sex-matched participants as a control group. We determined and compared nesfatin-1, GLP-1, total antioxidant status (TAS), and total oxidant status (TOS) levels in patients with PD and control group.ResultsThe mean GLP-1 and nesfatin-1 values of patients with PD were lower than those of the control group, whereas their mean TOS value was higher. The mean TAS values, on the other hand, did not reveal any significant difference between the patient and the control groups.ConclusionThe lower nesfatin-1 and GLP-1 levels, in addition to higher TOS levels, in patients with PD compared to those of control group suggest that the neuroprotective effects of these molecules might be related to the oxidative processes. Further studies are required to search for the impact of abovenamed molecules on the treatment option and the likelihood that they may slow down disease progression. Mugla Sitki Kocman University Research Projects Coordination OfficeMugla Sitki Kocman University [15/237] Mugla Sitki Kocman University Research Projects Coordination Office through Project Grant. Number has granted this paper: (15/237)

Nesfatin-1 is a novel anorexic peptide hormone that also exerts cardiovascular protective effects in rodent models. However, nesfatin-1 treatment at high doses also exerts vasopressor effects, which potentially limits its therapeutic application. Here, we evaluated the vasoprotective and vasopressor effects of nesfatin-1 at different doses in mouse models. Wild-type mice and those with the transgene nucleobindin-2, a precursor of nesfatin-1, were employed. Wild-type mice were randomly assigned to treatment with vehicle or nesfatin-1 at 0.2, 2.0 or 10 μg/kg/day (Nes-0.2, Nes-2, Nes-10, respectively). Subsequently, mice underwent femoral artery wire injury to induce arterial remodeling. After 4 weeks, injured arteries were collected for morphometric analysis. Compared with vehicle, nesfatin-1 treatments at 2.0 and 10 μg/kg/day decreased body weights and elevated plasma nesfatin-1 levels with no changes in systolic blood pressure. Furthermore, these treatments reduced neointimal hyperplasia without inducing undesirable remodeling in injured arteries. However, nesfatin-1 treatment at 0.2 μg/kg/day was insufficient to elevate plasma nesfatin-1 levels and showed no vascular effects. In nucleobindin-2-transgenic mice, blood pressure was slightly higher but neointimal area was lower than those observed in littermate controls. In cultured human vascular endothelial cells, nesfatin-1 concentration-dependently increased nitric oxide production. Additionally, nesfatin-1 increased AMP-activated protein kinase phosphorylation, which was abolished by inhibiting liver kinase B1. We thus demonstrated that nesfatin-1 treatment at appropriate doses suppressed arterial remodeling without affecting blood pressure. Our findings indicate that nesfatin-1 can be a therapeutic target for improved treatment of peripheral artery disease.

Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

Our study aimed to evaluate the impact of nesfatin-1 administration on bone metabolism and properties in established osteopenia in ovariectomized female rats. In total, 21 female Wistar rats were assigned to two groups: sham-operated (SHAM, n = 7) and ovariectomized (OVA, n = 14). After 12 weeks of osteopenia induction in the OVA females, the animals were given i.p. physiological saline (OVA, n = 7) or 2 µg/kg body weight of nesfatin-1(NES, n = 7) for the next 8 weeks. The SHAM animals received physiological saline at the same time. Final body weight, total bone mineral density and content of the skeleton were estimated. Then, isolated femora and tibias were subjected to densitometric, tomographic, and mechanical tests. Bone metabolism markers, i.e., osteocalcin, bone specific alkaline phosphatase (bALP), and crosslinked N-terminal telopeptide of type I collagen (NTx) were determined in serum using an ELISA kit. Ovariectomy led to negative changes in bone metabolism associated with increased resorption, thus diminishing the densitometric, tomographic, and mechanical parameters. In turn, the administration of nesfatin-1 led to an increase in the value of the majority of the tested parameters of bones. The lowest bALP concentration and the highest NTx concentration were found in the OVA females. The bALP concentration was significantly higher after nesfatin-1 administration in comparison to the OVA rats. In conclusion, the results indicate that nesfatin-1 treatment limits bone loss, preserves bone architecture, and increases bone strength in condition of established osteopenia.

Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune chronic neurological disease. Currently, there are no effective serum biomarkers to verify MS diagnosis, to assess disease prognosis, and evaluate response to MS treatment. Objective: The present study is a preliminary assessment of irisin and nesfatin-1 serum levels in patients with relapsing- remitting MS (RRMS). Methods: A total of 86 participants, 42 patients with RRMS diagnosis and 44 healthy controls were included in the study. The serum irisin and nesfatin-1 parameters of the patients and control group members were analyzed. Results: Irisin and nesfatin-1 levels of the RRMS patients were significantly lower than the controls (z: -3.82, p

Diabetic retinopathy (DR) is a major complication of diabetes mellitus that may cause severe visual impairment. It has been reported that the levels of nesfatin-1 in the serum and vitreous humor were negatively correlated with DR; however, its role in DR has not been fully elucidated. Therefore, the present study was performed to investigate the effect of nesfatin-1 on high glucose-treated human retinal epithelial cells (ARPE-19) and explore the underlying mechanism. The effects of nesfatin-1 on cell viability, inflammation, oxidative stress and apoptosis were examined under high glucose conditions. The Cell Counting Kit-8 assay was used to determine cell viability. The levels of inflammatory cytokines were evaluated using ELISA kits. The reactive oxygen species and malondialdehyde content was estimated using commercial assay kits. Flow cytometry was performed to detect apoptotic cells and western blot analysis was employed to evaluate the expression of apoptosis-associated proteins. Moreover, the levels of NF-κB, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and high-mobility group protein B1 (HMGB1) were determined via western blot analysis. The results revealed that nesfatin-1 enhanced cell viability and suppressed inflammation, oxidative stress and apoptosis in the presence of high glucose concentration. Moreover, the activation of the NF-κB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin-1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF-κB/NLRP3 inflammasome pathway caused by nesfatin-1. Taken together, these findings demonstrated that nesfatin-1 inhibited the activation of the NF-κB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE-19 cells against high glucose-induced inflammation, oxidative stress and apoptosis.

Nesfatin-1, a newly identified energy-regulating peptide, is widely expressed in the central and peripheral tissues, and has a variety of physiological activities. A large number of recent studies have shown that nesfatin-1 exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties and is involved in the occurrence and progression of various diseases. This review summarizes current data focusing on the therapeutic effects of nesfatin-1 under different pathophysiological conditions and the mechanisms underlying its antioxidant, anti-inflammatory, and anti-apoptotic activities.

Background Diabetes mellitus is the most common metabolic disorder worldwide. We aimed to determine the metabolic and clinical responses to Bunium Persicum (Black Caraway) supplementation in overweight and obese patients with T2DM. Methods Participant recruitment took place in the diabetic clinic of Bu-Ali hospital in Zahedan. Due to the eligibility criteria, 60 participants were randomly placed into two groups, namely placebo (n = 30) and BP (n = 30). The supplementation was considered one 1000 mg capsule 2 times /day BP by meals (lunch and dinner) for 8 weeks. Physical activity levels, dietary intakes, anthropometric measurements [weight, height, and waist circumference], glycemic indices [fasting blood glucose (FBG) and insulin (FBI)], blood lipids [triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c)], and serum nesfatin-1 level were determined. Homeostasis model assessment-insulin resistance (HOMA-IR), Quantitative insulin sensitivity checks index (QUICKI), and Body Mass Index (BMI) were computed. Results In comparison with placebo, BP significantly decreased FBG, HOMA-IR, and BMI (P ). The differences in the FBI, QUICKI, TG, TC, LDL, HDL, WC, and Nesfatin-1 were not significant (P > 0.05). Conclusion BP supplementation improved serum glucose indices and BMI among overweight and obese T2DM patients. Further trials are needed to confirm results. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20181207041876N1, Registered 18/01/2019, https://irct.ir/trial/35752

Objective This study aims to investigate the levels of nesfatin-1-hormone in patients with Antisocial Personality Disorder (ASPD) and their relationship with clinical variables.Methods A total of 90 people (45 ASPD, 45 controls) were included in our study. Sociodemographic Data Form, Beck-Depression-Inventory (BDI), Beck-Anxiety-Inventory (BAI), Barratt Impulsivity Scale (BIS-11), Buss-Durkee-Hostility-Inventory (BDHI) were applied to all participants. Venous blood samples were taken from participants at the same time of the day when they were hungry.Results It was found that the BDI and BAI scores of the ASPD were higher than those of the controls (p0.05).Conclusion This is the first study to examine the nesfatin-1-hormone levels in patients with any personality disorder. Further studies with more participants are needed in different types of personality disorders to understand the relationship between personality disorder and nesfatin-1-hormone levels.

Background Nonalcoholic fatty liver disease (NAFLD) is a serious and widespread disease worldwide. Bariatric surgery is one of the treatments for NAFLD. Nesfatin-1 is located in the brain, periphery and plasma. We studied the relationship between nesfatin-1 changes after laparoscopic sleeve gastrectomy (LSG) and NAFLD remission. Methods A total of 29 patients participated in the study, which collected clinical information on the patients and indicators of liver function, hepatic steatosis score and nesfatin-1 level before and after LSG. Results The average BMI of the patients before surgery was 42.63±8.91 kg/m2, and the average BMI was 28.54±5.63 kg/m2 one year after surgery (p

Ya-Yun Xu,1,2 Jin-Fang Ge,3 Jun Liang,1,2 Yin Cao,1,2 Feng Shan,1,2 Yang Liu,1,2 Chun-Yu Yan,1,2 Qing-Rong Xia1,2 1Department of Pharmacy, Hefei Fourth People’s Hospital, Hefei 230022, China; 2Psychopharmacology Laboratory, Anhui Mental Health Center, Hefei 230032, China; 3Anhui Key Laboratory of Bioactivity of Natural Products, School of Pharmacy, Anhui Medical University, Hefei 230032, China Background: This study aimed to determine whether plasma nesfatin-1, cortisol, and inflammatory cytokines could be used as novel noninvasive biomarkers for the diagnosis of moderate and severe depressive disorder (MSDD). Materials and methods: A total of 70 patients with MSDD and 70 healthy subjects were assessed. Patients with MSDD were selected from Hefei Fourth People’s Hospital, Anhui Mental Health Center, and subjects in the control group were selected from healthy volunteers. Hamilton Depression Rating Scale-17 (HAMD-17) was used to evaluate the two groups. ELISA was used for the measurement of plasma nesfatin-1, cortisol, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) levels. The diagnostic value of plasma nesfatin-1, cortisol, IL-6, CRP, and TNF-α for MSDD was assessed. Results: Compared to healthy controls, the HAMD-17 scores and average nesfatin-1, cortisol, IL-6, and CRP levels in patients with MSDD were significantly increased. Moreover, multivariate linear regression analysis showed that HAMD-17 score was positively associated with plasma nesfatin-1 and cortisol. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.985 with 94.3% sensitivity and 97.1% specificity of nesfatin-1, and an AUC of 0.957 with 91.4% sensitivity and 85.7% specificity of cortisol in discriminating patients with MSDD from healthy volunteers. A combined ROC analysis using nesfatin-1 and cortisol revealed an AUC of 0.993 with a sensitivity of 97.1% and a specificity of 98.6% in separating patients with MSDD from healthy volunteers. Conclusion: These results suggest that plasma nesfatin-1 and cortisol might be potential novel biomarkers for the diagnosis of MSDD. Keywords: C-reactive protein, cortisol, IL-6, depression, nesfatin-1, tumor necrosis factor-&alpha

This study aimed to investigate the potential effects of acute soccer matches performed in morning, afternoon and at night on both nesfatin-1 and irisin levels in trained subjects. Total of 20 male subjects performed in soccer matches at three different times of day: morning, afternoon, and night. Pre- and post-match venous blood samples were taken, and levels of both nesfatin-1 and irisin were analysed using the enzyme-linked immunosorbent assay (ELISA). Following all matches, the subjects' irisin levels increased significantly in all subjects (p < 0.0001). Nesfatin-1 levels were also increased after the matches; however, the increase was statistically significant for morning (P=0.01) and night-time (p=0.009). The subjects' nesfatin-1 levels did not increase in all subjects and decrease of nesfatin-1 levels observed in some subjects after matches. This study finds that soccer matches performed different workout times have strong stimulatory effects on irisin levels in all subjects but nesfatin-1 response varied among the subjects and it did not change significantly in afternoon match.

Background Despite of its significant therapeutic effects on obesity and metabolic diseases, Roux-en-Y gastric bypass (RYGB) has limited clinical application because of considerable impacts on the gastrointestinal structure and postoperative complications. This study aims to develop a simplified surgical approach with less damage and complication but efficient metabolic benefit. Methods The effects of Esophagus-Duodenum gastric bypass (EDGB) on body weight, food intake, glucose and lipid metabolism were compared to RYGB in mice. Findings EDGB is simple, has higher survival rate and less complication. Relative to RYGB, EDGB demonstrated modest body weight control, identical improvement of glucose and lipid metabolism in obese mice. Blood glucose increased significantly 15 and 30 min after oral glucose administration, then markedly decreased in both EDGB and RYGB groups relative to the sham surgery, indicating a quicker absorption of oral glucose and improvement in glucose uptake by insulin targeted tissues. Insulin sensitivity was identically improved. EDGB significantly decreased plasma and hepatic triglyceride levels, while increased browning in visceral and subcutaneous white adipose tissue to the extent identical to RYGB. Levels of ghrelin and nesfatin-1 increased significantly after EDGB and RYGB. Interpretation EDGB is a valuable model to study the metabolic benefit of bariatric surgery in mice., Highlights • Esophagus-Duodenum gastric bypass surgery is easier and safer to perform in mice. • Esophagus-Duodenum gastric bypass can produce a metabolic benefit as efficient as Roux-en-Y gastric bypass. • EDGB may serve as an alternative model to study the weight-loss-independent mechanisms for glycemic control. A valuable bariatric surgery designated as esophagus-duodenum gastric bypass surgery is easier and safer to perform. Post-operative complications are rare and survival rate is higher. The benefits to reduce bodyweight and improve blood glucose are identical to the commonly used bariatric surgery named Roux-en-Y gastric bypass surgery. In addition, esophagus-duodenum gastric bypass surgery improves lipid profile in the extent identical to Roux-en-Y gastric bypass surgery. Our study indicates that esophagus-duodenum gastric bypass surgery may provide an alternative approach for the intervention of obesity, and its associated metabolic dysfunctions such as diabetes and fatty liver.

AIM To establish a rat model of anxiety-like gastric hypersensitivity (GHS) of functional dyspepsia (FD) induced by novel sequential stress. METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood (8 wk) at which point the anxiety-like behaviors and visceromotor responses to gastric distention (20-100 mmHg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1A receptor (5-HT1AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined. RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequential-stress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT (51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA (2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF (304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1 (1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT (47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF (257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it (1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT (41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF (226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site (1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC (Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB (0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01) (n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.

Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland.

Both nesfatin-1 and cannabinoid systems involved in the regulation of sleep, metabolism, and food intake. The relationship between cannabinoid system and nesfatin-1 levels remains to be elucidated. This study investigated nesfatin-1 and insulin resistance in 72-h rapid eye movement (REM) sleep-deprived mice under the effects of cannabinoid, and cannabinoid receptors CB1R and CB2R blocking. Sixty mice were exposed to 72-h sleep deprivation. Groups and drug administrations were as follows: Group 1 (control) received injection of vehicle. Group 2 received WIN 55,212,2. Group 3 received AM251 (CB1R antagonist) followed by WIN 55,212,2 injection. Group 4 received SR144528 (CB2R antagonist) followed by WIN 55,212,2 injection. Group 5 received only AM251. Group 6 received only SR144528. Blood samples were collected 1 h after drug administration and prepared for biochemical measurements. Glucose levels were measured by glucometer, whereas insulin and nesfatin-1 levels were measured by ELISA. Central nesfatin-1 was also assessed using immunohistochemistry. One-way analysis of variance together with post hoc Tukey's test was used for inter-group comparisons. Serum nesfatin-1 levels were comparable in all study groups. Brain nesfatin-1 immune-positive cell count was lower in WIN group compared to controls. The administration of CB1R or CB2R antagonist prevented reduction in nesfatin-1-positive cell count. Insulin resistance was higher in WINCB2 and CB2 groups than in control and WINCB1 groups. Cannabinoid treatment reduced nesfatin-1 immunoreactivity in the central nervous system and this effect was prevented by either CB1R or CB2R antagonist pretreatment. Insulin resistance might be related to CB2 receptor activation which was independent from central nesfatin-1 immunoreactivity.

KISA, Ucler/0000-0002-8131-6810 WOS: 000466105100009 PubMed: 31023053 OBJECTIVES: To investigate the use of nesfatin-1 and caspase-cleaved cytokeratin-18 serum levels as biomarkers in Alzheimer's disease. METHODS: The study group consisted of 39 patients with Alzheimer's disease (AD) and 39 controls. Demographic characteristics including gender, age, body mass index, mini-mental status examination (MMSE) and duration of disease were recorded. The ELISA method was used to measure serum nesfatin-1 and CCCK-18 levels in serum samples. RESULTS: Serum nesfatin-1 levels were statistically significantly higher in the AD patient group than in controls. There was no significant difference between the groups with regards to serum CCCK-18 levels. Pearson analysis showed no significant correlation between serum nesfatin-1, serum CCCK-18 levels, mini-mental status examination and disease duration. CONCLUSION: This study proved that serum nesfatin-1 levels can be used as a biomarker in Alzheimer's disease by showing a statistically significant high level of serum nesfatin-1 in patients with Alzheimer's disease. This is the first study to suggest that nesfatin-1 can be used as a biomarker in Alzheimer's disease. In addition, our study showed that CCCK-18 can be used as a prognostic biomarker for Alzheimer's disease. Further comprehensive studies should be done to clarify the use of serum nesfatin-1 and CCCK-18 levels as biomarkers for Alzheimer disease (Tab. 3, Fig. 2, Ref. 25). Kirikkale UniversityKirikkale University This study was funded by Kirikkale University with this title Financial support and sponsorship.

Neuropeptides are involved in various brain activities being able to control a wide spectrum of higher mental functions. The purpose of this concise structural investigation was to detect the possible immunoreactivity of the novel multifunctional neuropeptide nesfatin-1 within the human bed nucleus of the stria terminalis (BNST). The BNST is involved in the mechanism of fear learning, integration of stress and reward circuits, and pathogenesis of addiction. Nesfatin-1-expressing neurons were identified for the first time in several regions of the BNST using both immunohistochemical and fluorescent methods. This may implicate a potential contribution of this neuropeptide to the BNST-related mechanisms of stress/reward responses in the human brain.

Nucb2 is a multifunctional protein associated with a variety of biological processes. Multiple studies have revealed that Nucb2, and its derivative nesfatin-1, are involved in carcinogenesis. Interestingly, the role of Nucb2/nesfatin-1 in tumorigenesis seems to be dual—both pro-metastatic and anti-metastatic. The implication of Nucb2/nesfatin-1 in carcinogenesis seems to be tissue dependent. Herein, we review the role of Nucb2/nesfatin-1 in both carcinogenesis and the apoptosis process, and we also highlight the multifaceted nature of Nucb2/nesfatin-1.

Ghrelin, and nesfatin-1 (encoded by nucleobindin2/nucb2) are two metabolic peptides with multiple biological effects in vertebrates. While sex steroids are known to regulate endogenous ghrelin and NUCB2 in mammals, such actions by steroids in fish remain unknown. This study aimed to determine whether estradiol (E2) and testosterone (T) affects the expression of preproghrelin, ghrelin/growth hormone secretagogue receptor (GHS-R), ghrelin O-acyl transferase (GOAT) and NUCB2 in goldfish (Carassius auratus). First, a dose-response assay was performed in which fish were intraperitoneally (ip) implanted with pellets containing 25, 50 or 100 μg/g body weight (BW) of E2 or T. It was found that sex steroids (100 μg/g BW) administered for 2.5 days achieved the highest E2 or T in circulation. In a second experiment, fish were ip implanted with pellets containing 100. μg/g BW of E2, T or without hormone (control). RT-qPCR analyses at 2.5 days post-administration show that gut preproghrelin and GOAT expression was upregulated by both E2 and T treatments, while the same effect was observed for GHS-R only in the pituitary. Both treatments also reduced hypothalamic preproghrelin mRNA expression. NUCB2 expression was increased in the forebrain of T treated group and reduced in the gut and pituitary under both treatments. These results show for the first time a modulation of preproghrelin and nucb2/nesfatin-1 by sex steroids in fish. The interaction between sex steroids and genes implicated in both metabolism and reproduction might help meeting the reproduction dependent energy demands in fish. Fil: Bertucci, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina Fil: Blanco, Ayelén Melisa. Universidad Complutense de Madrid; España Fil: Canosa, Luis Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina Fil: Unniappan, Suraj. University of Saskatchewan; Canadá

Nesfatin-1 is an anorexic peptide derived from a precursor, nucleobindin-2 (NUCB2), which is distributed in various organs, coexists with ghrelin in the gastric X/A-like cells and closely relates to an appetite control in rodents and humans. Nesfatin-1 may be a significant factor addressing the satiety also in veterinary medicine, however, there are few reports about nesfatin-1 in dogs. In the present study, we detected canine NUCB2/nesfatin-1 mRNA in various tissues, especially abundant in pancreas, gastrointestinal tracts, testis and cerebellum. We examined circulating nesfatin-1 concentrations and NUCB2/nesfatin-1 mRNA expressions in upper gastrointestinal tracts (gastric corpus, pyloric antrum and duodenum) in dogs fed on different types of diets. Plasma nesfatin-1 concentrations in the dogs were approximately 4 ng/ml and they did not change after feeding through the study, however, NUCB2/nesfatin-1 mRNA expressions in pyloric antrum were 1.84-fold higher in the dogs fed on a High fiber/High protein diet (P

The pregnancy and abortion process involves a complex mechanism with various immune cells present in the implantation sites and several hormones associated with pregnancy, such as leptin, ghrelin and nesfatin-1. However, the mechanism underlying spontaneous abortion by maternal T helper 17 (Th17) present in the implantation sites and nesfatin-1, which is of anorexigenic hormones, is not fully understood so far. Therefore, the purpose of this study was to examine the possible roles of Th17 cells present in the implantation sites and nesfatin-1 expressed in the uterus on spontaneous abortion using the CBA/j × DBA/2 mouse model. Th17 transcription factor, ROR-γt mRNA expression was significantly increased in the abortion sites compared with the implantation sites of abortion model mice on day 14.5 and 19.5 of pregnancy. In addition, the expression levels of IL(-1)7A mRNA were significantly higher in abortion sites than in implantation sites on day 14.5 and 19.5. Moreover, the nesfatin-1/NUCB2 protein and mRNA levels were increased in abortion sites compared with levels in implantation sites of both normal pregnant and abortion model mice on day 14.5 of pregnancy. Interestingly, nesfatin- 1/NUCB2 serum levels were not changed throughout the whole pregnancy in abortion model mice, but its serum level was dramatically increased on day 14.5, and then rapidly decreased on day 19.5 in normal pregnant mice. In this study, we showed for the first time the expression of nesfatin-1/NUCB2 mRNA and protein in implantation sites during pregnancy. The present results suggest that Th17 cells in the uterus may play an important role in the period of implantation and for maintenance of pregnancy. Furthermore, the present results suggest that Th17 cells in implantation sites may be a key regulator for maintenance of pregnancy and provides evidence that activation of these cells may be regulated by nesfatin-1/NUCB2. Further study is needed to elucidate the role of nesfatin-1 expressed in the uterus during pregnancy.

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications, however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer&rsquo, s instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.

Background The incidence of depressive symptoms is higher in cancer patients. And depression can also affect the occurrence, development and outcome of cancer through the neuroendocrine-immune-network system. Objective To study the level of Nesfatin-1 in the plasma and brain tissue and its role in the pathogenesis in gastric cancer comorbid with depression using a mouse gastric cancer model. Methods 18 mice were randomly divided into the normal control group (NCG), gastric cancer without stress model group (GCNS), and gastric cancer combined with stress model group (GCS). The mice of the GCNS group were inoculated subcutaneously with mouse forestomach carcinoma (MFC) after 5 weeks of nomal feeding to establish a model of subcutaneous transplantation tumor. After 5 weeks of chronic unpredicted mild stress (CUMS) in the GCS group, subcutaneous inoculation of MFC was used to establish a subcutaneous transplantation tumor model for 1 week. Evaluation of mice behavior was performed by open field test, sucrose preference test and forced swimming test (FST). Determination of Nesfatin-1 concentration in plasma and brain tissue was carried out using enzyme linked immunosorbent assay (ELISA) and Western Blot. Results The weight increment in the GCS group was significantly lower than that in the GCNS group (t=-3.39, p

Objective: Malnutrition continues to be a leading cause of stunted growth in many countries. This study aimed to investigate serum nesfatin-1 and orexin-A levels in underweight children and the potential correlations of these levels with anthropometric and nutritional parameters. Methods: The study enrolled 44 prepubertal children (between 2 and 12 years of age) with thinness grades of 1-3 and 41 healthy age- and gender-matched children. The demographic, clinical and laboratory parameters including nesfatin-1 and orexin-A concentrations were compared between the two groups. The correlations of nesfatin-1 and orexin-A with biochemical and anthropometric parameters were investigated. The receiver operating characteristic (ROC) analysis were also performed for evaluating nesfatin-1 and orexin-A in distinguishing children with malnutrition from healthy controls. Results: Thyroid-stimulating hormone, vitamin B12 and insulin levels were significantly lower in the study group than controls (p=0.001, p=0.049 and p=0.033, respectively). Mean nesfatin-1 levels in the malnourished group was also significantly lower compared to the healthy controls (3871.2 ± 1608.8 vs. 5515.0 ± 3816.4 pg/mL, p=0.012). No significant difference was observed in the orexin-A levels between the two groups (malnourished vs. control groups: 1135.7 ± 306.0 vs. 1025.7 ± 361.6 pg/mL, p=0.141). Correlation analyses revealed a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index (BMI) z-score. ROC analysis demonstrated that nesfatin-1 and orexin-A cannot be used to distinguish children with malnutrition from healthy controls (AUC: 0.620, p=0.061 for nesfatin-1 and AUC: 0.584, p=0.190 for orexin-A). Conclusion: The positive correlation of nesfatin-1 and the negative correlation of orexin-A with BMI suggest that these neuropeptides may be a part of a protective mechanism in the maintenance of nutritional status and that they may have a role in regulating food intake in undernourished children.

In this study, we aimed to determine the role of a novel peptide – nesfatin 1- in appetite control and define its anorectic mechanism in order to reveal whether it can be used in fight against obesity. We reviewed the articles in the literature investigating the structure, mechanism of effect and experimental usefulness of nesfatin-1. We entered the word “nesfatin” to medical databases and reviewed the literature. Administration of nesfatin-1 maintains a significant reduce in food intake. Its effectiveness in rats is proven. More and more, new researches are in progress to determine its exact mechanism of effect. Nesfatin-1 is a satiety agent. However, use of nesfatin-1 as an anti-obesity agent in humans remains an unclarified field and needs further investigations. Turk Jem 2015; 19: 60-64

Aim: The aim of this study was to investigate the effect of nesfatin-1 signaling in the ventromedial hypothalamus (VMH) on gastric functions, as well as the regulation of these effects by nucleus accumbens (NAc) projections to VMH. Methods: The expression of c-fos in nesfatinergic VMH neurons induced by gastric distension (GD) was measured using the double fluoro-immunohistochemical staining. The firing rates of neurons were monitored with single-unit extracellular electric discharge recording. The projection of nesfatinergic neurons from NAc to VMH was observed by fluorogold retrograde tracer combined with fluoro-immunohistochemical staining. The effect of nesfatin-1 in VMH or electric stimulation in NAc on gastric function was studied by measuring food intake, gastric acid output, gastric motility, and gastric emptying, and the ability of the melanocortin-3/4 receptor antagonist SHU9119 or the anti-nesfatin-1 antibody to block nesfatin-1 in the VMH was assessed. Results: Expression of c-fos was observed in VMH nesfatinergic neurons following GD in rats. Further, nesfatin-1 delivery to single GD-responsive neurons changed the firing rates of these neurons in the VMH. In awake, behaving rats, intra-VMH administration of nesfatin-1 inhibited food intake, gastric acid output, gastric motility, and gastric emptying. These effects were abolished by SHU9119. Fluorogold retrograde tracing showed nesfatinergic neural projection from the NAc to the VMH. Electrical stimulation of NAc modified the firing rates of the VMH neurons and inhibited food intake and gastric functions. The pretreatment with an anti-nesfatin-1 antibody in the VMH reversed the effects of NAc electrical stimulation on the VMH neuronal firing rates and gastric function. Conclusions: Nesfatin-1 in the VMH inhibited food intake, gastric acid output, gastric motility, and gastric emptying. A nesfatinergic pathway between NAc and VMH transmitted metabolism-regulating signals.

Purpose: Nesfatin-1 is a recently discovered energy-regulating peptide, widely expressed in both central and peripheral tissues. It is involved in various functions, such as the stimulation of hypothalamic-pituitary-adrenal axis and sympathetic nervous system, influencing visceral functions, water intake, and regulation of temperature and emotions. It exerts a direct glucose-dependent insulinotropic action on the beta cells of pancreatic islets. The current study evaluated nesfatin-1 levels and insulin response to glucose load in patients with impaired glucose tolerance (IGT) and in healthy subjects. Material and Method: Of those patients who underwent the oral glucose tolerance test (OGTT), 14 with IGT and 13 body mass index-(BMI) and age-matched healthy subjects as controls were included in the study. Blood samples were taken at 0, 60 and 120 min, and the glucose, insulin, and nesfatin-1 levels were measured. Results: The basal levels of glucose, insulin, and nesfatin-1 were significantly higher in the patients with IGT than in controls. Two-way repeated measures ANOVA revealed that change in time (CIT) for glucose and insulin during an OGTT was significant (p

NUCB2/nesfatin-1 has been implicated in various physiological functions such as feeding, drinking and the sleep-wake cycle, but its effect on epileptic activity is not clear. The aim of this study was to investigate the effects of NUCB2/nesfatin-1 on penicillin-induced epileptic activity and to answer the question of whether only NUCB2/nesfatin-1 cause epileptic activity in rats. Thirty-five rats were randomly assigned to the following seven groups: control, saline, penicillin, two different doses of NUCB2/nesfatin-1 (100 and 300 pmol), penicillin and two different doses of NUCB2/nesfatin-1 (100 and 300 pmol). EEGs were recorded before the injections and during the following 120 min. The EEG and motor findings of epileptic seizures were observed in NUCB2/nesfatin-1-injected groups. NUCB2/nesfatin-1 significantly increased the EEG power spectrum, spike frequency and amplitude values in penicillin-induced epileptic rats. These findings indicate that NUCB2/nesfatin-1 both causes epileptic activity and increases penicillin-induced epileptic activity in rats. © Springer Science+Business Media New York 2014.