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Nesfatin-1, a newly identified energy-regulating peptide, has been reported to possess antioxidant, anti-inflammatory, and antiapoptotic properties; however, to date, its effect on rheumatoid arthritis (RA) has not been previously explored in detail. We previously showed that activation of acid-sensing ion channel 1a (ASIC1a) by acidosis plays an important role in RA pathogenesis. Therefore, in this study, we evaluated the effects of nesfatin-1 on acidosis-stimulated chondrocyte injury in vitro and in vivo and examined the involvement of ASIC1a and the mechanism underlying the effects of nesfatin-1 on RA. Acid-stimulated articular chondrocytes were used to examine one of the several possible mechanisms underlying RA pathogenesis in vitro. The mRNA expression profile of acid-induced chondrocytes treated or not treated with nesfatin-1 was investigated by RNA sequencing. The effects of nesfatin-1 on oxidative stress, inflammation, and apoptosis in acid-induced chondrocytes were measured. The mechanistic effect of nesfatin-1 on ASIC1a expression and intracellular Ca

Nucleobindin2 (NUCB2) is a member of nucleobindin family which was first found in the nucleus of the hypothalamus, and had a relationship in diet and energy homeostasis. Its location in normal tissues such as stomach and islet further confirms that it plays a vital role in the regulation of physiological functions of the body. Besides, NUCB2 participates in tumorigenesis through activating various signal-pathways, more and more studies indicate that NUCB2 might impact tumor progression by promoting or inhibiting proliferation, apoptosis, autophagy, metastasis, and invasion of tumor cells. In this review, we comprehensively stated NUCB2's expression and functions, and introduced the role of NUCB2 in physiology and pathology and its mechanism. What is more, pointed out the potential direction of future research.

Background: Nesfatin-1 is a newly identified satiety peptide that has regulatory effects on food intake and glucose metabolism, and is located in the hypothalamic nuclei, including the supraoptic nucleus (SON). In this study, we have investigated the hypothesis that nesfatin-1 neurons are activated by refeeding and intraperitoneal (ip) glucose injection and that the glutamatergic system has regulatory influences on nesfatin-1 neurons in the SON. Materials and methods: The first set of experiments analyzed activation of nesfatin-1 neurons after refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: fasting group, refeeding group and antagonist (CNQX+refeeding) group. The second set of experiments analyzed activation of nesfatin-1 neurons by glucose injection as a metabolic stimulus and the effectiveness of the glutamatergic system on this metabolic stimulation. The subjects were randomly divided into three groups: saline group, glucose group and antagonist (CNQX+glucose) group. Results: Refeeding significantly increased the number of activated nesfatin-1 neurons by approximately 66%, and intraperitoneal glucose injection activated these neurons by about 55%, compared to the fasting and saline controls. The injections of glutamate antagonist (CNQX) greatly decreased the number of activated nesfatin-1 neurons. Conclusions: This study suggested that nesfatin-1 neurons were activated by peripheral and/or metabolic signals and that this effect was mediated through the glutamatergic system.

Xiaoping Wu,1,2,* Biao Dai,2,3,* Fanfan Yan,1,2 Yang Chen,2,4 Yayun Xu,5 Qingrong Xia,2,6 Xulai Zhang1,2 1Department of Geriatric Psychology, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Medical Education and Research, Anhui Mental Health Center, Hefei, People’s Republic of China; 3Department of Pharmacy, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Modified Electroconvulsive Therapy Room, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230032, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 6Department of Science and Education, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xulai Zhang, Department of Geriatric Psychology, Hefei Fourth People’s Hospital, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Hefei, 230032, People’s Republic of China, Tel +86 551 63616022, Fax +86 551 63616022, Email Xulaizhang@ahmhcentre.comAim: Treatment-resistant depression (TRD) affects approximately 30% of patients with major depressive disorder (MDD), especially elderly patients. As individuals with TRD are at an increased risk of committing suicide and pose a higher risk of relapse, early diagnostic biomarkers of TRD and a better understanding of the resistance mechanism are highly needed. This study aimed to determine whether serum cortisol, nesfatin-1, and pro-inflammatory cytokines can be used as biomarkers for the diagnosis of elderly patients with TRD.Methods: Thirty elderly patients with TRD were selected as the TRD group. Thirty elderly patients with MDD who were effectively treated with conventional antidepressants were selected as the non-TRD group. The baseline levels of serum cortisol, nesfatin-1, and pro-inflammatory cytokines were measured and compared, and their diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating patients with TRD from those without TRD.Results: Serum cortisol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were significantly higher in the non-TRD and TRD groups than in the control group. Moreover, serum cortisol, CRP, TNF-α, and IL-6 levels in the TRD group were significantly lower than those in the non-TRD group. Furthermore, serum nesfatin-1 levels in the non-TRD group were significantly lower than those in the control and TRD groups, while the serum IL-1β levels in the non-TRD group were significantly higher than those in the control and TRD groups. Additionally, an ROC analysis revealed an area under the curve (AUC) of 0.929 for the combination of nesfatin-1 and IL-1β and an AUC of 0.956 for the combination of cortisol, nesfatin-1, and IL-1β in discriminating elderly patients with TRD from those without non-TRD.Conclusion: Serum cortisol, nesfatin-1, and IL-1β may be potential diagnostic biomarkers for discriminating elderly patients with TRD from those without TRD.Keywords: treatment-resistant depression, nesfatin-1, cortisol, pro-inflammatory cytokine, diagnosis, elderly

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.

Nesfatin-1, an anorexic neuropeptide discovered in 2006, is widely distributed in the central nervous system and peripheral tissues. It has been shown to be involved in the regulation of food intake and lipid metabolism, inhibiting fat accumulation, accelerating lipid decomposition, and in general, inhibiting the development of lipid-related diseases, such as obesity and metabolic syndrome. Potential mechanisms of Nesfatin-1 action in lipid metabolism and lipid-related diseases will be discussed as well as its role as a biomarker in cardiovascular disease. This review expected to provide a new strategy for the diagnosis and prevention of clinically related diseases.

The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1β) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1β in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1β synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1β in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.

Nesfatin-1, the cleavage product of nucleobindin-2, is an anorexigenic peptide and major regulator of energy homeostasis. Beyond reducing food intake and increasing energy expenditure, it is also involved in regulating the stress response. Interaction of nucleobindin-2/nesfatin-1 and glucose homeostasis has been observed and recent findings suggest a link between the action of the antidiabetic drug metformin and the nesfatinergic system. Hence, this study aimed to clarify the role of nucleobindin-2/nesfatin-1 in the paraventricular nucleus of the hypothalamus in energy homeostasis as well as its involvement in stress- and metformin-mediated changes in energy expenditure. Knockdown of nucleobindin-2/nesfatin-1 in male Wistar rats led to significantly increased food intake, body weight, and reduced energy expenditure compared to controls. Nucleobindin-2/nesfatin-1 knockdown animals developed an obese-like phenotype represented by significantly increased fat mass and overall increase of circulating lipids. Concomitantly, expression of nucleobindin-2 and melanocortin receptor type 3 and 4 mRNA in the paraventricular nucleus was decreased indicating successful knockdown and impairment at the level of the melanocortin system. Additionally, stress induced activation of interscapular brown adipose tissue was significantly decreased in nucleobindin-2/nesfatin-1 knockdown animals and accompanied by lower adrenal weight. Finally, intracerebroventricular administration of metformin significantly increased energy expenditure in controls and this effect was absent in nucleobindin-2/nesfatin-1 knockdown animals. Overall, we clarified the crucial role of nucleobindin-2/nesfatin-1 in the paraventricular nucleus of the hypothalamus in the regulation of energy homeostasis. The nesfatinergic system was further identified as important mediator in stress- and metformin-induced thermogenesis.

The characteristic features of cancer cells are aberrant (acidic) intracellular pH and elevated levels of phosphatidylserine. The primary focus of cancer research is concentrated on the discovery of biomarkers directed towards early diagnosis and therapy. It has been observed that azoxymethane-treated mice demonstrate an increased expression of calnuc (a multi-domain, Ca2+- and DNA-binding protein) in their colon, suggesting it to be a good biomarker of carcinogenesis. We show that culture supernatants from tumor cells have significantly higher amounts of secreted calnuc compared to non-tumor cells, selectively packaged into exosomes. Exosomal calnuc is causal for epithelial–mesenchymal transition and atypical migration in non-tumor cells, which are key events in tumorigenesis and metastasis. In vitro studies reveal a significant affinity for calnuc towards phosphatidylserine, specifically to its C-terminal region, leading to the formation of ‘molten globule’ conformation. Similar structural changes are observed at acidic pH (pH 4), which demonstrates the role of the acidic microenvironment in causing the molten globule conformation and membrane interaction. On a precise note, we propose that the molten globule structure of calnuc caused by aberrant conditions in cancer cells to be the causative mechanism underlying its exosome-mediated secretion, thereby driving metastasis.

Spinal cord injury (SCI) is one of the most severe neurological diseases. However, there is still no effective treatment for it. Nesfatin, a precursor neuropeptide derived from nucleobindin 2 (NUCB2), has displayed a wide range of protective effects in different types of cells and tissue. However, the effects of nesfatin-1 in SCI have not been reported before.A SCI model was established. The behavior of mice was assessed using the Basso, Beattie, and Bresnahan (BBB) assessment.Here, we report that the administration of nesfatin-1 improved neurological recovery in SCI mice by increasing BBB scores, reducing lesion area volume and spinal cord water content. Also, nesfatin-1 ameliorated oxidative stress by reducing reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. We also found that nesfatin-1 prevented neuronal apoptosis in SCI mice by reducing caspase 3 activity and the expression of Bax, as well as increasing B-cell lymphoma-2 (Bcl-2). Additionally, nesfatin-1 reduced the levels of interleukin 6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Nesfatin-1 also promoted microglia towards M2 polarization by increasing the marker CD206 but reducing CD16. Importantly, nesfatin-1 enhanced the phosphorylation of signal transducer and activator of transcription 1 (STAT1) but reduced the expression levels of toll-like receptor 4 (TLR4) and phosphorylated nuclear factor kappa-B p65 (p-NF-κB p65).Our findings imply that nesfatin-1 exerts neuroprotective actions in SCI by promoting the activation of M2 microglia, and its underlying mechanisms might be related to the activation of STAT1 and inhibition of the TLR4/NF-κB signaling pathway.

Nesfatin-1, a newly discovered adipokine derived from nucleobindin-2 (NUCB2), has been described as a new prognostic marker in cancers. This study aimed to explore the functional role of NUCB2/nesfatin-1 in the cell proliferation, migration and invasion in gastric carcinoma (GC). The expressions of NUCB2/nesfatin-1 in GC tissues and normal adjacent tissues (NATs) were compared, and the effect of inhibition of NUCB2/nesfatin-1 on the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in GC cell line SGC-7901 was investigated. Cell transfection was conducted to inhibit NUCB2/nesfatin-1 by short hairpin RNA. Cell proliferation, migration and invasion abilities were determined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing and transwell assays, respectively. The expressions of EMT markers E-Cadherin and N-Cadherin were determined using western blotting. The expression of NUCB2/nesfatin-1 protein in GC tissues was significantly increased compared with that in NATs. Consistently, the serum concentrations of NUCB2/nesfatin-1 were significantly higher in patients with GC as compared with those in the control group. Moreover, the results of CCK-8 assay and EdU assay indicated that knockdown of NUCB2/nesfatin-1 could markedly decrease SGC-7901 proliferation. Furthermore, the results of wound healing assay and transwell assay demonstrated that knockdown of NUCB2/nesfatin-1 significantly suppressed SGC-7901 migration and invasion abilities. Additionally, knockdown of NUCB2/nesfatin-1 decreased the expressions of N-Cadherin and increased the expressions of E-Cadherin in SGC-7901 cells. These findings suggest that knockdown of NUCB2/nesfatin-1 suppressed the proliferation, migration, invasion and EMT of SGC-7901 cells, suggesting a potentially promising therapeutic target for GC.

Nesfatin-1 and -2 are produced from a reaction in which the N-terminus of human Nucleobindin-2 undergoes proteolytical processing. To date, Nucleobindin-2 and/or nesfatin-1 have only been shown to act as peptide hormones. On the other hand, the purpose of nesfatin-2 remains unknown. Since Nucleobindin-2/nesfatin-1 is thought impact the control of a wide range of physiological processes, including energy homeostasis, neurodegenerative processes and carcinogenesis, its ligands/interactions deserve special studies and attention. However, there are no reports about the molecular properties of the proteolytical products of human Nucleobindin-2 in the literature. Hence, this study aimed to analyze the effect of Zn(II) and Ca(II) on human nesfatin-1, -2, and -1/2 structures. Herein, we report that human nesfatin-1 is a member of the intrinsically disordered protein family, as indicated by circular dichroism and analytical ultracentrifugation experiments. In contrast, we found that the human nesfatin-2 and nesfatin-1/2 structures were globular with intrinsically disordered regions. Under Zn(II) treatment, we observed concentration-dependent structurization and compaction of intrinsically disordered nesfatin-1 and its propensity for oligomerization, as well as destabilization of both nesfatin-2 and nesfatin-1/2. Furthermore, dissociation constants for Zn(II) binding by nesfatin-1, nesfatin-2, and nesfatin-1/2 were also reported. Moreover, structurally distinct nesfatin-1 and -2 seem to be interdependent when linked together, as indicated by the observed molecular properties of nesfatin-1/2, which in turn are not a simple sum of the properties exhibited by the former peptides. Thus, herein, we shed new light on the molecular behavior of human nesfatins, which might help to elucidate the complex function of those peptides.

Nesfatin-1 is a novel anorexigenic peptide that possesses antihyperglycemic and cardiovascular effects. We hypothesized that nesfatin-1 has a beneficial protective effect against diabetic cardiomyopathy (DC). We investigated the therapeutic effect of nesfatin-1 on diabetes-associated cardiac dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mouse model. We found that the cardiac nesfatin-1 level was lower in diabetic mice than in normal mice. Nesfatin-1 treatment (180 mg/kg/day for two weeks) improved insulin sensitivity and mitigated diabetic dyslipidemia. Nesfatin-1 ameliorated the diabetes-related myocardial hypertrophy and heart dysfunction, as revealed by the reduced hypertrophy index, heart rate, mean arterial pressure (MAP), creatine kinase (CK)-MB, and aspartate aminotransferase (AST) levels. Nesfatin-1 exerted antioxidant and anti-inflammatory activity in diabetic mice, as shown by decreased reactive oxygen species (ROS), oxidative lipid product malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH), decreased cardiac and plasma interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) levels. Mechanistically, we found that nesfatin-1 inhibited the cardiac p38-MAPK pathway activation and subsequent glucagon-like peptide-1 (GLP-1) level. Collectively, our data shows nesfatin-1 exerted protective effects against diabetic cardiomyopathy. Our study suggests that nesfatin-1 therapy has therapeutic implications against diabetic cardiomyopathy.

Nesfatin‐1 (encoded by NUCB2) is a cardiac peptide possessing protective activities against myocardial ischaemia/reperfusion (MI/R) injury. However, the regulation of NUCB2/nesfatin‐1 and the molecular mechanisms underlying its roles in MI/R injury are not clear. Here, by investigating a mouse MI/R injury model developed with transient myocardial ischaemia followed by reperfusion, we found that the levels of NUCB2 transcript and nesfatin‐1 amount in the heart were both decreased, suggesting a transcriptional repression of NUCB2/nesfatin‐1 in response to MI/R injury. Moreover, cardiac nesfatin‐1 restoration reduced infarct size, troponin T (cTnT) level and myocardial apoptosis, supporting its cardioprotection against MI/R injury in vivo. Mechanistically, the Akt/ERK pathway was activated, and in contrast, endoplasmic reticulum (ER) stress was attenuated by nesfatin‐1 following MI/R injury. In an in vitro system, similar results were obtained in nesfatin‐1‐treated H9c2 cardiomyocytes with hypoxia/reoxygenation (H/R) injury. More importantly, the treatment of wortmannin, an inhibitor of Akt/ERK pathway, abrogated nesfatin‐1 effects on attenuating ER stress and H/R injury in H9c2 cells. Furthermore, nesfatin‐1‐mediated protection against H/R injury also vanished in the presence of tunicamycin (TM), an ER stress inducer. Lastly, Akt/ERK inhibition reversed nesfatin‐1 effects on mouse ER stress and MI/R injury in vivo. Taken together, these findings demonstrate that NUCB2/nesfatin‐1 inhibits MI/R injury through attenuating ER stress, which relies on Akt/ERK pathway activation. Hence, our study provides a molecular basis for understanding how NUCB2/nesfatin‐1 reduces MI/R injury.

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 as a new energy-regulating peptide has been known to display a pivotal role in modulation of cardiovascular functions and protection against ischemia/reperfusion injury. However, the detailed knowledge about molecular mechanisms underlying this protection has not been completely investigated yet. This study was designed to clarify the molecular mechanisms by which nesfatin-1 exert cardioprotection effects against myocardial ischemia-reperfusion (MI/R). Left anterior descending coronary artery (LAD) was ligated for 30 min to create a MI/R model in rats. MI/R rats were treated with three concentrations of nesfatin-1 (10, 15 and 20 µg/kg) then expression of necroptosis and necrosis mediators were measured by western blotting assay. Fibrosis, morphological damages, cardiac function, myocardial injury indictors and oxidative stress factors were evaluated as well. Induction of MI/R model resulted in cardiac dysfunction, oxidative stress, increased activity of RIPK1-RIPK3-MLKL axis and RhoA/ROCK pathway, extension of fibrosis and heart tissue damage. Highest tested concentration of nesfatin-1 markedly improved cardiac function. Moreover, it reduced oxidative stress, collagen deposition, and morphological damages, through inhibiting the expression of necroptosis mediators and also, necrosis including RIPK1, RIPK3, MLKL, ROCK1, and ROCK2 proteins. The lowest and middle tested concentrations of nesfatin-1 failed to exert protective effects against MI/R. These findings have shown that nesfatin-1 can exert cardioprotection against MI/R in a dose dependent manner by suppressing necroptosis via modulation of RIPK1-RIPK3-MLKL axis and RhoA/ROCK/RIP3 signaling pathway.

Background: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor arising in the nasopharynx. MicroRNAs (miRNAs) are elucidated to exert tumor-suppressing function in human cancers. Numerous studies have manifested that miR-30a-5p serves as an anti-oncogene in various cancers. Objective: To research the biological function and molecular mechanism of miR-30a-5p in NPC. Methods: The morphology of NPC tissues was revealed by H&E staining. Transwell and wound healing assays were applied to investigate the effects of miR-30a-5p on NPC cell migration. The binding interaction between miR-30a-5p and nucleobindin 2 (NUCB2) was identified by luciferase reporter assay. Xenograft nude mice were used to detect the influence of miR-30a-5p on NPC tumor growth. Results: MiR-30a-5p was downregulated in NPC tissues and cells. The overexpression ofmiR-30a-5p inhibited proliferation, migration and invasion abilities of NPC cells. Moreover, NUCB2 was revealed to be a downstream target gene of miR-30a-5p, and knockdown of NUCB2 repressed the malignant behaviors of NPC cells and tumor growth. Additionally, rescue experiments revealed that miR-30a-5p suppressed the proliferation, migration and invasion of NPC cells via targeting NUCB2 in vitro. Meanwhile, in vivo assays depicted that NUCB2 overexpression rescued the effects induced by miR-30a-5p upregulation on tumor growth. Conclusion: MiR-30a-5p modulates NPC progression by targeting NUCB2. These findings lay a foundation for exploring the clinical treatment of NPC.

Nesfatin-1 (NES1) is a potential biomarker found in serum and saliva that indicates hyperpolarization and depolarization in the hypothalamic ventricle nucleus as well as an increase in epileptic conditions. However, real-time investigations have not been carried out to detect changes in the concentration of NES1. In this study, we develop a multiscale pore contained carbon nanofiber-based field-effect transistor (FET) biosensor to detect NES1. The activated multiscale pore contained carbon nanofiber (a-MPCNF) is generated using a single-nozzle co-electrospinning method and a subsequent steam-activation process to obtain a signal transducer and template for immobilization of bioreceptors. The prepared biosensor exhibits a high sensitivity to NES1. It can detect levels as low as 0.1 fM of NES1, even in the presence of other interfering biomolecules. Furthermore, the a-MPCNF-based FET sensor has significant potential for practical applications in non-invasive real-time diagnosis, as indicated by its sensing performance in artificial saliva.

NUCB2/nesfatin-1 was originally discovered as an anorexigenic peptide. However, recent studies revealed various additional functions including the regulation of inflammation. However, there are no studies that investigated the involvement of NUCB2/nesfatin-1 in neuroinflammatory diseases. Here, we aimed to investigate the involvement of NUCB2/nesfatin-1 in a representative neuroinflammatory disease, multiple sclerosis (MS). Cerebrospinal fluids (CSF) were collected from 24 MS patients and 10 control subjects and NUCB2/nesfatin-1, proinflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, TGF-β) levels were measured by using ELISA assay. Also the expression of NUCB2/nesfatin-1 in the CSF of MS patient was investigated by western blot analysis. Expression of NUCB2/nesfatin-1 was confirmed in the CSF of the MS patient by western blot analysis. NUCB2/nesfatin-1 levels were significantly higher in the CSF of the MS patients. Among the measured cytokines, only IL-1β was lower in the CSF of the MS patients. We report for the first time increased NUCB2/nesfatin-1 levels in the CSF of MS patients.

Aims: We aimed to investigate putative neuroprotective effects of nesfatin-1 on oxidative brain injury and memory dysfunction induced by a single epileptic seizure and to compare these effects with those of antiepileptic phenytoin. Main methods: Wistar albino rats were randomly divided into a control group and pentylenetetrazole (PTZ)-seizure groups pretreated intraperitoneally (ip) with saline or nesfatin-1 (NES-1; 0.3, 1 or 3 μg/kg/day) or phenytoin (PHE; 40 mg/kg/day) or PHE + NES-1 (0.3 μg/kg/day) at 30 min before the single-dose PTZ injection (45 mg/kg; ip). All treatments were repeated at the 24th and 48th h of the provoked epileptic seizure. Passive-avoidance test was performed to assess memory function. The rats were decapitated at the 72nd hour of seizures and brain tissues were analyzed for histopathological changes and for measuring levels of malondialdehyde, glutathione, myeloperoxidase activity and reactive oxygen/nitrogen species. Key findings: In parallel to the effects of phenytoin, NES-1 reduced seizure score, elevated antioxidant glutathione content, depressed generation of nitric oxide and protected against seizure-induced neuronal damage. Additionally, increased malondialdehyde levels and elevated glial fibrillary acidic protein immunoreactivity in the cortex and hippocampus were decreased and memory dysfunction was improved by NES-1. However, NES-1 had no impact on myeloperoxidase activity or production of reactive oxygen species in the brain. Significance: The findings of the present study demonstrate that nesfatin-1 treatment provides neuroprotection against seizure-induced oxidative damage and memory dysfunction by inhibiting reactive nitrogen species and upregulating antioxidant capacity, indicating its potential in alleviating memory deficits and increasing the effectiveness of conventional anti-convulsant therapies. © 2022 2-s2.0-85124233306 35123998

Data Availability Statement: Data are available via the corresponding authors upon reasonable request that does not raise any ethical, privacy, or security concerns. Copyright: © 2022 by the authors. Background: Excess adipose tissue accumulation and obesity are characterised by chronic, low-grade, systemic inflammation. Nestfatin-1 is a neuropeptide derived from the precursor protein nucleobindin-2 (NUCB2), which was initially reported to exert anorexigenic effects. The present study aimed to investigate the effects of an obesogenic diet (OD; high-fat, high-sugar) in NUCB2 knockout (KO) mice and of nesfatin-1 treatment in LPS-stimulated 3T3-L1 preadipocytes. Methods: Subcutaneous white adipose tissue (Sc-WAT) samples from wild type (WT) and NUCB2 KO mice that were fed a normal diet (ND), or the OD for 12 weeks were used for RNA and protein extraction, as well as immunohistochemistry. 3T3-L1 cells were treated with 100 nM nesfatin-1 during differentiation and stimulated with 1 µg/mL LPS for measuring the expression and secretion of pro-inflammatory mediators by qPCR, western blotting, immunofluorescence, Bioplex, and ELISA. Results: Following the OD, the mRNA, protein and cellular expression of pro-inflammatory mediators (Tnfα, Il-6, Il-1β, Adgre1, Mcp1, TLR4, Hmbgb1 and NF-kB) significantly increased in the ScWAT of NUCB2 KO mice compared to ND controls. Adiponectin and Nrf2 expression significantly decreased in the ScWAT of OD-fed NUCB2 KO, without changes in the OD-fed WT mice. Furthermore, nesfatin-1 treatment in LPS-stimulated 3T3-L1 cells significantly reduced the expression and secretion of pro-inflammatory cytokines (Tnfα, Il-6, Il-1β, Mcp1) and hmgb1. Conclusion: An obesogenic diet can induce significant inflammation in the ScWAT of NUCB2 KO mice, involving the HMGB1, NRF2 and NF-kB pathways, while nesfatin-1 reduces the pro-inflammatory response in LPS-stimulated 3T3-L1 cells. These findings provide a novel insight into the metabolic regulation of inflammation in WAT. This research received no external funding.

AimModified electroconvulsive therapy (MECT) is an effective strategy for treatment-resistant depression (TRD); however, the mechanism underlying effects of MECT remains unclear. Accumulating evidence suggests that TRD is closely associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, anorexigenic peptides, and pro-inflammatory cytokines. However, MECT effects on the HPA axis, anorexigenic peptides, and pro-inflammatory cytokines in elderly patients with TRD remain unclear. In this study, we investigated whether the HPA axis (cortisol), anorexigenic peptides (nesfatin-1), and pro-inflammatory cytokines (C-reactive protein, tumor necrosis factor-α, and interleukin-6, and interleukin-1β) are involved in the mechanism underlying MECT effects in elderly patients with TRD.MethodsElderly patients with TRD were enrolled in this study between December 2019 and October 2021; all patients underwent MECT after physical examination. Serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels were measured before and after the first, third, and sixth MECT sessions. The Hamilton Depression Rating Scale-24 (HAMD-24) and the Mini-Mental State Examination (MMSE) were used to evaluate depression and cognitive impairment, respectively. We compared pre- and post-MECT serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels to confirm the short-term effects of MECT on these serum indices. We compared these serum indices across three time points (before the first, third, and sixth MECT sessions) to determine the long-term effects of MECT on serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels.ResultsWe observed no statistically significant changes in the pre- and post-MECT serum cortisol, nesfatin-1, or pro-inflammatory cytokine levels. No significant changes in serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels were observed across the aforementioned time points. Moreover, there were no statistically significant sex-based differences in the aforementioned serum indices. Furthermore, the serum cortisol level was negatively correlated with the serum IL-6 level before and after the first MECT session in patients with high cortisol levels (> the 50th percentile value of all samples). Additionally, the post-MECT HAMD-24 and MMSE scores were significantly lower.ConclusionsMECT reduced depressive symptoms despite an adverse effect on cognition and had no significant effect on the serum cortisol, nesfatin-1, and pro-inflammatory cytokine levels in elderly patients with TRD.

Preeclampsia (PE) is a leading cause of perinatal and maternal mortality. Considering that Nesfatin-1 was reported to be downregulated in serum of PE patients, we aimed to explore the functional role of Nesfatin-1 in trophoblast cells. Cell transfection was conducted to overexpress or inhibit Nesfatin-1, and its expression was measured by quantitative PCR. Cell proliferation, migration, and invasion abilities were determined employing CCK-8, flow cytometry, wound-healing, and transwell assays. Immunofluorescence assay was performed to detect E-cadherin and vimentin. ROS, MDA, and SOD levels were measured using their corresponding commercial kits. Western blot was used to identify the expression of vital kinases in PI3K/AKT/mTOR or GSK3β pathway and invasion-related proteins in trophoblast cells. Nesfatin-1 knockdown significantly suppressed proliferation, migration, and invasion and increased cell arrest in G1 phase, as well as downregulated expressions of MMP2/9 in HTR-8/SVneo cells. Besides, Nesfatin-1 knockdown promoted the expression of E-cadherin and reduced the expression of vimentin. Additionally, the levels of ROS, MDA, and SOD were elevated upon Nesfatin-1 knockdown. On the contrary, Nesfatin-1 overexpression exerted the opposite effects. Nesfatin-1 promoted the activation of PI3K/AKT/mTOR or GSK3β pathway, blocking of which reversed the promotive effects on trophoblast invasion and the inhibitory effects on oxidative stress of Nesfatin-1 in HTR-8/SVneo cells. In short, this study revealed that Nesfatin-1 promoted trophoblast cell proliferation, migration, invasion, and EMT and suppressed oxidative stress by activating PI3K/AKT/mTOR and AKT/GSK3β signaling pathway, laying the foundation for the development of therapeutic strategy for PE by targeting Nesfatin-1.

The effective treatment of polycystic ovary syndrome (PCOS)-related hormonal disorders necessitates the development of novel treatment strategies. Resveratrol is found in certain food products, and is known to exhibit phytoestrogen properties. The present study was to assess whether resveratrol exhibits beneficial phytoestrogenic effects and associated hormonal modulation in a rat model of PCOS.This model was established by administering oral letrozole to female Sprague-Dawley (SD) rats prior to randomizing them into control, model and resveratrol treatment groups (40, 80, or 160 mg/kg). Animals were treated for 30 days, after which time ovarian tissues were collected and evaluatedWe found that resveratrol administration was associated with increased levels of plasma adiponectin and estradiol levels and restoration of normal ovarian morphology in PCOS model animals. In addition, this treatment was linked to the increased ovarian expression of nesfatin-1 and aromatase at the RNA and protein levels.Together things findings suggest that resveratrol may represent an effective tool for treating PCOS owing to its phytoestrogenic properties.

Nesfatin-1, a pleotropic peptide, was recently implicated in the regulation of anxiety and depression-like behavior in rats. However, the underlying mechanisms remain unclear so far. Thus, this study aimed to investigate the role of endogenous nesfatin-1 in the mediation of anxiety and depression-like behavior induced by corticotropin-releasing factor (CRF). Therefore, normal weight male intracerebroventricularly (icv) cannulated Sprague Dawley rats received two consecutive icv injections of anti-nesfatin-1 antibody or IgG control antibody followed by CRF or saline, before being exposed to a behavioral test. In the elevated zero maze test, assessing anxiety and explorative behavior, blockade of nesfatin-1 using an anti-nesfatin-1 antibody under basal conditions increased the number of entries into the open arms compared to control antibody/vehicle (1.6-fold, p 0.05) and the time in open arms compared to the other groups (p 0.05). Control antibody/CRF-treated animals tended to spend less time in the open arms compared to control antibody/vehicle (0.7-fold, p = 0.17), an effect not altered by the nesfatin-1 antibody (control antibody/CRF-treated animals vs. nesfatin-1 antibody/CRF group, p = 1.00). In the novelty-induced hypophagia test, assessing anhedonia as part of depression-like behavior, no significant differences were observed between the four groups for the latency to the first bout, number of bouts and the amount of palatable snack eaten (p 0.05). In summary, CRF tended to increase anxiety and explorative behavior an effect not altered by blockade of nesfatin-1, whereas no significant effect of CRF on anhedonia was observed. Blockade of endogenous nesfatin-1 significantly decreased anxiety-like behavior giving rise to a physiological role of brain nesfatin-1 in the mediation of anxiety.

Objective Recent studies have investigated the circulating adipocyte fatty acid binding protein (FABP4), nesfatin-1, and osteocalcin (OC) concentrations in women diagnosed with gestational diabetes mellitus (GDM), but the findings prove to be conflicting. The objective of this research was to systematically assess the relationship of circulating levels of above adipokines with GDM. Methods Pubmed, Embase, Web of Science, Cochrane library, OVID, and Scopus were performed to locate articles published up to January 31, 2020. Pooled standard mean differences (SMDs) with 95% confidence intervals (CIs), and 95% predictive intervals (PIs) were calculated by random-effects models to compare levels of adipokines between GDM cases and control groups. Cumulative and single-arm meta-analyses were also performed. Results Thirty-one studies comprising 4590 participants were included. No significant differences were found between GDM women and healthy controls in circulating nesfatin-1 levels (4.56 vs. 5.02 ng/mL; SMD = − 0.11, 95% CI -0.61–0.38, 95% PI -1.63–1.41). Nevertheless, circulating FABP4 and OC levels observed in GDM women outnumbered normal controls (FABP4, 23.68 vs. 16.04 ng/mL; SMD = 2.99, 95% CI 2.28–3.69, 95% PI 0.28–5.71; OC, 52.34 vs. 51.04 ng/mL; SMD = 0.68, 95% CI 0.31–1.05, 95% PI -0.48–1.84). The cumulative meta-analysis showed that the SMDs of circulating FABP4 and OC levels had stabilized between the two groups. Conclusions Elevated circulating FABP4 and OC levels were observed in GDM women, but nesfatin-1 levels did not change, the PI of OC crossed the no-effect threshold. The results suggested that FABP4 is more suitable as a biomarker of GDM compared to OC in a future study, which is useful in identifying pregnant women who are likely to develop GDM and providing prompt management strategies.

Nesfatin-1 is the proteolytic cleavage product of Nucleobindin 2, which is expressed both in a number of brain nuclei (e. g., the paraventricular nucleus of the hypothalamus) and peripheral tissues. While Nucleobindin 2 acts as a calcium binding protein, nesfatin-1 was shown to affect energy homeostasis upon central nervous administration by decreasing food intake and increasing thermogenesis. In turn, Nucleobindin 2 mRNA expression is downregulated in starvation and upregulated in the satiated state. Still, knowledge about the physiological role of endogenous Nucleobindin 2/nesfatin-1 in the control of energy homeostasis is limited and since its receptor has not yet been identified, rendering pharmacological blockade impossible. To overcome this obstacle, we tested and successfully established an antibody-based experimental model to antagonize the action of nesfatin-1. This model was then employed to investigate the physiological role of endogenous Nucleobindin 2/nesfatin-1. To this end, we applied nesfatin-1 antibody into the paraventricular nucleus of satiated rats to antagonize the presumably high endogenous Nucleobindin 2/nesfatin-1 levels in this feeding condition. In these animals, nesfatin-1 antibody administration led to a significant decrease in thermogenesis, demonstrating the important role of endogenous Nucleobindin 2/nesfatin-1in the regulation of energy expenditure. Additionally, food and water intake were significantly increased, confirming and complementing previous findings. Moreover, neuropeptide Y was identified as a major downstream target of endogenous Nucleobindin 2/nesfatin-1.

Nucleobindin-2 (Nucb2) is a widely expressed multi-domain protein. Nucb2 participates in many physiological processes, i.e. calcium level maintenance, feeding regulation in the hypothalamus, emotion and stress regulation, and many others. To date, this protein has not been structurally characterized. We describe the first comparative structural analysis of two homologs, a Gallus gallus and a Homo sapiens Nucb2. The in silico analysis suggested that apo-Nucb2s contain a mosaic-like structure, consisting of intertwined disordered and ordered regions. Surprisingly, the hydrogen-deuterium exchange mass spectrometry results revealed that Nucb2 is divided into two parts: an N-terminal half with a stable mosaic-like structure and a disordered C-terminal half. However, the presence of Ca2+ induces the formation of a mosaic-like structure in the C-terminal half of the Nucb2s. The Ca2+ also affects the tertiary and quaternary structure of Nucb2s. The presence of Ca2+ leads to an overall compaction of the Nucb2 molecule, resulting in structural change that is propagated along the molecule, which in turn affects the quaternary structure of the protein. Intrinsic disorder, and the mosaic-like Ca2+ dependent structure of Nucb2s, might be seen as the molecular factors responsible for their multifunctionality. Thus, Nucb2s might function as the versatile Ca2+ sensor involved in signal transduction.

This study aimed to investigate the role of leptin, ghrelin, neuropeptide Y, and nesfatin-1 in young children with autism spectrum disorder (ASD). A total of 44 children with ASD and 44 healthy controls aged 18-60 months were included. Plasma levels of hormones were measured using commercial enzyme-linked immunosorbent assay kits. Plasma leptin and ghrelin levels were significantly higher in the ASD group than in the control group. However, no significant difference for plasma neuropeptide Y and nesfatin-1 levels was detected between the groups. No relation was found between the severity of ASD symptoms, severity of eating problems, and plasma levels of hormones. Leptin and ghrelin may play a potential role in the pathogenesis of ASD.

Nucleobindin (Nucb)-1 and Nucb2 are DNA and Ca2+ binding proteins with multiple functions in vertebrates. Prohormone convertase-mediated processing of Nucb2 results in the production of biologically active nesfatin-1. Nesfatin-1 is involved in the regulation of reproduction in many vertebrates, including fish. Our lab originally reported a nesfatin-1-like peptide (Nlp) encoded in Nucb1 that exhibits nesfatin-1-like metabolic effects. We hypothesized that Nlp has a suppressive role in the reproductive physiology of fish. In this research, whether Nlp regulates reproductive hormones and oocyte maturation in fish were determined. Single intraperitoneal (IP) injection of goldfish Nlp (50 ng/g body weight) suppressed salmon and chicken gonadotropin-releasing hormone (sgnrh and cgnrh2), gonadotropin-inhibiting hormone (gnih) and its receptor (gnihr), and kisspeptin and brain aromatase mRNA expression in the hypothalamus of both male and female goldfish. In the pituitary, Nlp decreased mRNAs encoding lhb, fshb and kisspeptin and its receptor, while a significant increase in gnih and gnihr was observed. In the gonads, lh (only in male fish) and fsh receptor mRNAs were also significantly downregulated in Nlp-injected fish. Sex-specific modulation of gnih, gnihr, and kisspeptin system in the gonads was also observed. Nlp decreased sex steroidogenic enzyme encoding mRNAs and circulating levels of testosterone and estradiol. In addition, incubation of zebrafish ovarian follicles with Nlp resulted in a reduction in oocyte maturation. These results provide evidence for a robust role for Nlp in regulating reproductive hormones in goldfish and oocyte maturation in zebrafish, and these effects resemble that of nesfatin-1.Summary SentenceNesfatin-1-like peptide is a negative modulator of reproduction in goldfish.

Zdecydowana większość nowych neuropeptydów posiada unikalne właściwości biochemiczne, a także szerokie spectrum aktywności fizjologicznej realizowane w licznych szlakach neuronalnych, w tym w podwzgórzu i w układzie limbicznym. Szczególnie wartym uwagi wydaje się stosunkowo niedawno odkryty i wciąż intensywnie badany czynnik regulatorowy i potencjalny modulator zachowań żywieniowych nesfatyna-1. Szereg nowych informacji na temat tego neuropeptydu pozwala obecnie uznać go za potencjalnie istotny czynnik zaangażowany w patogenezę szeregu zróżnicowanych zaburzeń psychicznych. Nie należy zatem wykluczyć, że rozważana farmakomodulacja sygnalizacji tego neuropeptydu może być potencjalnie pomocna w przyszłym leczeniu pewnych zaburzeń neuropsychiatrycznych i metabolicznych takich jak jadłowstręt psychiczny. Na dzień dzisiejszy wyniki stosunkowo licznych badań podstawowych i klinicznych wydają się być obiecujące niemniej wszelkie możliwe zastosowania wyżej wymienionych neuropeptydów, a także ich agonistów i antagonistów nadal pozostają w obszarze spekulacji. Intensywne poszukiwanie selektywnych modulatorów ich znanych receptorów jest jednak uzasadnione i może przyczynić się do otwarcia obiecującego rozdziału w terapii zaburzeń odżywiania. W niniejszym artykule dokonano przeglądu najnowszych doniesień dotyczących hipotetycznej roli nesfatyny-1 w szlakach neuronalnych związanych z patofizjologią jadłowstrętu psychicznego.

NUCB1 and NUCB2, two novel nucleobindins, have attracted extensive attention for their role in the appetite regulation in mammals. However, little is known about the appetite regulation of NUCB1 and NUCB2 in fish species. Therefore, we investigated the role of these peptides in the regulation of feeding in Schizothorax davidi (S. davidi). In this study, full-length cDNA sequences of nucb1 and nucb2A of S. davidi were obtained for the first time. Additionally, the tissue distribution and the effects of different energy status on nucb1 and nucb2A mRNAs abundance were assessed, showing that nucb1 and nucb2A are widely distributed in 18 detected tissues, with the highest expression in the cerebellum. The abundances of nucb1 and nucb2A increased in the hypothalamus at 1 h and 3 h post-feeding. Furthermore, fasting and re-feeding experiments showed that the expressions of nucb1 and nucb2A in hypothalamus significantly decreased after fasting for 7 days, and returned to the control level after re-feeding for 3 or 5 days. In conclusion, the present study suggests that both NUCB1 and NUCB2A are involved in the short-term and long-term appetite regulation, as an anorexigenic factor, in S. davidi. These results can provide a basis for further investigation into the appetite regulatory role of NUCB family in teleost.

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.

Objective The aim of the study was to determine the effect of nesfatin-1 on bone properties in female rats in the conditions of developing osteopenia induced by ovariectomy (OVX). Material and methods The experiment was performed on 21 female Wistar rats assigned to 3 groups receiving intraperitoneally physiological saline (SHO, OVX-PhS) and nesfatin-1 in dose 2 μg/kg BW of (OVX-NES) once a day for 8 wks. At the end of the experiment, the rats were scanned using the DXA method to determine the body composition, tBMC, and tBMD. The isolated femora and tibia were tested with the DXA method for BMD and BMC, and with the pQCT method for separate analysis of the cortical and trabecular bone tissue. The bone strength parameters were also determined. The immunohistochemical method was used for determination of nesfatin-1 localization in growth cartilage. Bone metabolism markers (osteocalcin, bALP, and NTx) were identified using an ELISA kit. Results OVX exerts a negative effect on bone tissue. The nesfatin-1 administration influenced positively the DXA parameters of tibia. TvBMD and TbvBMD measured by pQCT in metaphysis of bones were significantly higher in the OVX-NES group than in OVX-PhS. No differences were found in the values of bone strength parameters between SHO and OVX-NES females. Extra- and intracellular immunohistochemical reaction for nesfatin-1 was observed in all zones of growth cartilage, with the strongest reaction detected in the calcifying zone. Nesfatin-1 administration caused a significant increase in the osteocalcin and bALP concentration in relation to the OVX-PhS animals. Conclusions The results of the experiment indicate that nesfatin-1 exerts a protective effect on bone tissue properties and can be used in the prevention of osteoporosis.