The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction.

Ghrelin and nesfatin-1 are enteroendocrine peptide hormones expressed in rat X/A-like and human P/D1cells of the gastric mucosa. Besides their effect on food intake, both peptides are also implicated in various other physiological systems. One of these is the reproductive system. This present review illustrates the distribution of ghrelin and nesfatin-1 along the hypothalamus-pituitary-gonadal (HPG) axis, their modulation by reproductive hormones, and effects on reproductive functions as well as highlighting gaps in current knowledge to foster further research.

Nesfatin-1 stimulates the hypothalamus-pituitary-interrenal axis hormones in goldfish.

Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.

Beneficial phytoestrogenic effects of resveratrol on polycystic ovary syndromein rat model.

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

Effects of feeding status on nucb1 and nucb2A mRNA expression in the hypothalamus of Schizothorax davidi.

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.

Genetic analyses uncover pleiotropic compensatory roles for Drosophila Nucleobindin-1 in inositol trisphosphate-mediated intracellular calcium homeostasis.

Nucleobindin-1 is an EF-hand calcium-binding protein with a distinctive profile, predominantly localized to the Golgi in insect and wide-ranging vertebrate cell types, alike. Its putative involvements in intracellular calcium (Ca2+) homeostasis have never been phenotypically characterized in any model organism. We have analyzed an adult-viable mutant that completely disrupts the G protein α-subunit binding and activating (GBA) motif of Drosophila Nucleobindin-1 (dmNUCB1). Such disruption does not manifest any obvious fitness-related, morphological/developmental, or behavioral abnormalities. A single copy of this mutation or the knockdown of dmnucb1 in restricted sets of cells variously rescues pleiotropic mutant phenotypes arising from impaired inositol 1,4,5-trisphosphate receptor (IP3R) activity (in turn depleting cytoplasmic Ca2+ levels across diverse tissue types). Additionally, altered dmNUCB1 expression or function considerably reverses lifespan and mobility improvements effected by IP3R mutants, in a Drosophila model of amyotrophic lateral sclerosis. Homology modeling-based analyses further predict a high degree of conformational conservation in Drosophila, of biochemically validated structural determinants in the GBA motif that specify in vertebrates, the unconventional Ca2+-regulated interaction of NUCB1 with Gαi subunits. The broad implications of our findings are hypothetically discussed, regarding potential roles for NUCB1 in GBA-mediated, Golgi-associated Ca2+ signaling, in health and disease.

Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats.

Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.

Eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin in rats.

The hypothalamus controls metabolism and feeding behaviour via several signals with other tissues. Exercise and supplements can change hypothalamic signalling pathways, so the present study investigated the influence of eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid supplementation on PGC-1α expression, serum irisin, nesfatin-1 and resistin concentrations. Thirty-two male rats (8 weeks old, 200±17 g body mass) were randomly allocated to control, ß-hydroxy-ß-methylbutyrate free acid supplementation (HMB), eccentric resistance training (ERT), and ß-hydroxy-ß-methylbutyrate free acid supplementation plus eccentric resistance training (HMB+ERT) groups. Training groups undertook eccentric resistance training (6 weeks, 3 times a week) and supplement groups consumed ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) orally (76 mg kg-1 day-1). Twenty-four hours after the last training session, serum and triceps brachii muscle samples were collected and sent to the laboratory for analysis. Two-way ANOVA and Pearson correlation were employed (significance level: P<0.05). The results showed that eccentric resistance training increases skeletal muscle PGC-1α gene expression, as well as serum levels of irisin and nesfatin-1 (P=0.001). Eccentric resistance training decreased the serum concentration of resistin (P=0.001). HMB-FA supplementation increased skeletal muscle PGC-1α gene expression (P=0.002), as well as the serum concentration of irisin and nesfatin-1 (P=0.001), but decreased the serum concentration of resistin (P=0.001). Significant correlations were observed between PGC-1α gene expression and serum concentrations of irisin, nesfatin-1 and resistin. HMB-FA supplementation with eccentric resistance training may induce crosstalk between peptide release from other tissues and increases maximal muscle strength. The combination of the two interventions had a more substantial effect than each in isolation.