NCBI Summary:
This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]
General function
Ligand, Growth factor
Comment
Cellular localization
Secreted
Comment
NUCB2/Nesfatin-1 in the Blood and Follicular Fluid in Patients with Polycystic Ovary Syndrome and Poor Ovarian Response. Catak Z et al. (2020) Failure to respond adequately to standard protocols and to recruit adequate follicles is called 'poor ovarian response'. The relationships between metabolic alterations and NUCB2/Nesfatin-1 levels were explored in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection. This case-control study involved 20 infertile women with PCOS and 20 control women diagnosed as poor ovarian responders stimulated with a GnRH antagonist. Blood samples were taken during ovum pick-up and follicular fluids (FF) were obtained from a dominant follicle from the subjects. Samples were analyzed by using ELISA. Statistical analysis was performed with SPSS version 20. Data are expressed as means ± standard deviation (SD). Blood NUCB2/Nesfatin-1 levels in PCOS were significantly lower (p= 0.011) while the NUCB2/Nesfatin-1 levels of FF in poor ovarian response (POR) were higher, but not statistically significant. Insulin, total testosterone, fasting glucose, homeostasis model assessment, and insulin resistance index in women with POR decreased when compared with PCOS. Blood NUCB2/Nesfatin-1 levels were significantly higher than FF NUCB2/Nesfatin-1 levels in both groups (p<0.001). Moreover, a positive correlation was detected between blood NUCB2/Nesfatin-1 and testosterone (p=0.602, r=0.304), HOMA-IR (p=0.252, r=0.384), BMI (p=0.880, r= 0.44) in PCOS, but it was not significant. NUCB2/Nesfatin-1 levels might be important in follicular growth in PCOS subjects undergoing IVF/ICSI with an antagonist protocol and NUCB2/Nesfatin-1 level could reliably help to predict poor ovarian response.//////////////////
Ovarian function
Steroid metabolism, Oocyte maturation
Comment
Potential physiological involvement of nesfatin-1 in regulating swine granulosa cell functions. Ciccimarra R et al. (2019) Nesfatin-1 has recently been indicated as a pleiotropic molecule that is primarily involved in the metabolic regulation of reproductive functions acting at hypothalamic level. The aim of this study was to explore the local action of nesfatin-1 in swine ovarian follicles. Nucleobindin 2 (NUCB2) was verified using real-time quantitative polymerase chain reaction in swine granulosa cells from different sized follicles and nesfatin-1 was localised by immunohistochemistry in sections of the whole porcine ovary. The effects of different concentrations of nesfatin-1 on cell growth, steroidogenesis and the redox status of granulosa cells were determined invitro. In addition, the effects of nesfatin-1 were evaluated in an angiogenesis bioassay because vessel growth is essential for ovarian follicle function. Immunohistochemistry revealed intense positivity for nesfatin-1 in swine granulosa cells in follicles at all developmental stages. Expression of the gene encoding the precursor protein NUCB2 was higher in granulosa cells from large rather than from medium and small follicles. Further, nesfatin-1 stimulated cell proliferation and progesterone production and interfered with redox status by modifying nitric oxide production and non-enzyme scavenging activity in granulosa cells from large follicles. Moreover, nesfatin-1 exhibited a stimulatory effect on angiogenesis. This study demonstrates, for the first time, that nesfatin-1 is physiologically present in the swine ovarian follicle, where it may impair granulosa cell functions.//////////////////
Stimulatory effects of NESFATIN-1 on meiotic and developmental competence of porcine oocytes. Cao Z et al. (2019) NESFATIN-1 acts as a neuroendocrine hormone to suppress gonadotropin secretion in the female goldfish and to prevent germinal vesicle breakdown of oocytes in the zebrafish. However, the expression and function of NESFATIN-1 in meiotic maturation and development of porcine oocytes remains elusive. Genomic structure of porcine NESFATIN-1 precursor nucleobindin 2 (NUCB2) is first characterized in detail and an evolutionally closer relationship of NESFATIN-1 between pig and rat is shown by phylogenetic analysis of multiple species. Additionally, immunofluorescence analysis revealed that NESFATIN-1 is predominantly expressed and localizes on the membrane of both theca cells and granulosa cells, but not expressed in oocytes. Real-time quantitative polymerase chain reaction showed that the abundance of NESFATIN-1 transcripts in granulosa cells progressively decreases during the developmental transition from small follicles to large follicles. Correspondingly, NESFATIN-1 could significantly enhance both the cleavage and blastocyst rate of parthenogenetically activated oocytes from small follicles (p < 0.05), whereas it did not affect meiotic maturation and development of oocytes from large follicles. Interestingly, we found that NESFATIN-1 significantly improves meiotic maturation of oocytes cultured in chemically defined medium in the absence of pyruvate compared with the control group (p < 0.05), suggesting that the NESFATIN-1 as a substitute for pyruvate exerts beneficial effects on porcine oocyte maturation. In conclusion, these results demonstrate that NESFATIN-1 facilitates both meiotic maturation and development of porcine oocytes.////////////////// Plasma nesfatin-1 levels are increased in patients with polycystic ovary syndrome. Ademoglu EN 2014 et al.
BACKGROUND
Nesfatin-1 is a recently discovered neuropeptide derived from its precursor nucleobindin-2 (NUCB2) and has been implicated in the regulation of feeding and energy metabolism. It is located in the brain and also produced at the periphery and present in the plasma. However, its pathophysiological role in humans remains unknown. Polycystic ovary syndrome (PCOS) is commonly presented with obesity, insulin resistance, hyperandrogenemia and hirsutism.
AIM
To characterize serum nesfatin-1 levels in PCOS women and determine association of nesfatin-1 with metabolic parameters.
MATERIALS AND METHODS
It is a cross-sectional study of 55 PCOS and 28 healthy women matched in age, in a university hospital setting. Anthropometric, hormonal, metabolic parameters and nesfatin-1 blood levels were determined.
RESULTS
Nesfatin-1 levels were significantly higher in PCOS group compared with the controls 371.43???2.50 versus 275.55???1.74?pg/mL. Multivariate logistic regression analysis that contains: nesfatin-1, body mass index and homeostasis model assessment index revealed significant correlation of nesfatin-1 with the existence of PCOS (p?
Expression regulated by
FSH
Comment
Gonadotropin regulates NUCB2/nesfatin-1 expression in the mouse ovary and uterus. Kim J et al. (2019) NUCB2/nesfatin-1 is expressed in the hypothalamus and regulates food intake and energy metabolism. Recent studies showed that NUCB2/nesfatin-1 also plays a role in other organs. However, its expression pattern and function in female reproductive organs are unclear. Therefore, we investigated NUCB2/nesfatin-1 expression in the ovary and uterus of mice and determined whether it is regulated by gonadotropins and sex steroid hormones. NUCB2 mRNA and nesfatin-1 protein were detected in the ovary and uterus of mice. NUCB2/nesfatin-1 expression in both organs was highest in the estrus period of the estrus cycle. Administration of pregnant mare serum gonadotropin (PMSG) dose-dependently increased mRNA expression of NUCB2 in the ovary and uterus of mice. On the other hand, mRNA expression of NUCB2 in the uterus was dramatically decreased after ovariectomy and was not increased upon administration of PMSG. Injection of 17β-estradiol upregulated mRNA expression of NUCB2 in the uterus of ovariectomized mice, whereas injection of progesterone did not. These results suggest that NUCB2/nesfatin-1 expression in the ovary and uterus of mice is regulated through the hypothalamus-pituitary-ovary axis and that NUCB2/nesfatin-1 is a local regulator of ovarian steroidogenesis and uterine function.//////////////////
Ovarian localization
Oocyte, Granulosa
Comment
PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte. Tang A et al. (2016) Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.//////////////////