Visfatin (NAMPT) affects global gene expression in porcine anterior pituitary cells during the mid-luteal phase of the oestrous cycle.

BACKGROUND: The pituitary belongs to the most important endocrine glands involved in regulating reproductive functions. The proper functioning of this gland ensures the undisturbed course of the oestrous cycle and affects the female's reproductive potential. It is believed that visfatin, a hormone belonging to the adipokine family, may regulate reproductive functions in response to the female's metabolic state. Herein we verified the hypothesis that suggests a modulatory effect of visfatin on the anterior pituitary transcriptome during the mid-luteal phase of the oestrous cycle. RESULTS: RNA-seq analysis of the porcine anterior pituitary cells revealed changes in the expression of 202 genes (95 up-regulated and 107 down-regulated in the presence of visfatin, when compared to the non-treated controls), assigned to 318 gene ontology terms. We revealed changes in the frequency of alternative splicing events (235 cases), as well as long noncoding RNA expression (79 cases) in the presence of the adipokine. The identified genes were associated, among others, with reproductive system development, epithelial cell proliferation, positive regulation of cell development, gland morphogenesis and cell chemotaxis. CONCLUSIONS: The obtained results indicate a modulatory influence of visfatin on the regulation of the porcine transcriptome and, in consequence, pituitary physiology during the mid-luteal phase of the oestrous cycle.

eNAMPT is a novel therapeutic target for mitigation of coronary microvascular disease in type 2 diabetes.

AIMS/HYPOTHESIS: Individuals with diabetes are at high risk of cardiovascular complications, which significantly increase morbidity/mortality. Coronary microvascular disease (CMD) is recognised as a critical contributor to the increased cardiac mortality observed in people with diabetes. Therefore, there is an urgent need for treatments that are specific to CMD. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern and TLR4 ligand, whose plasma levels are elevated in people with diabetes. This study was thus designed to investigate the pathogenic role of intracellular nicotinamide phosphoribosyltransferase (iNAMPT) and eNAMPT in promoting the development of CMD in a preclinical murine model of type 2 diabetes. METHODS: An inducible type 2 diabetic mouse model was generated by a single injection of low-dose streptozocin (75 mg/kg, i.p.) combined with a high-fat diet for 16 weeks. The in vivo effects of i/eNAMPT inhibition on cardiac endothelial cell (CEC) function were evaluated by using Nampt+/- heterozygous mice, chronic administration of eNAMPT-neutralising monoclonal antibody (mAb) or use of an NAMPT enzymatic inhibitor (FK866). RESULTS: As expected, diabetic wild-type mice exhibited significantly lower coronary flow velocity reserve (CFVR), a determinant of coronary microvascular function, compared with control wild-type mice. eNAMPT plasma levels or expression in CECs were significantly greater in diabetic mice than in control mice. Furthermore, in comparison with diabetic wild-type mice, diabetic Nampt+/- heterozygous mice showed markedly improved CFVR, accompanied by increased left ventricular capillary density and augmented endothelium-dependent relaxation (EDR) in the coronary artery. NAMPT inhibition by FK866 or an eNAMPT-neutralising mAb significantly increased CFVR in diabetic mice. Furthermore, administration of the eNAMPT mAb upregulated expression of angiogenesis- and EDR-related genes in CECs from diabetic mice. Treatment with either eNAMPT or NAD+ significantly decreased CEC migration and reduced EDR in coronary arteries, partly linked to increased production of mitochondrial reactive oxygen species. CONCLUSIONS/INTERPRETATION: These data indicate that increased i/eNAMPT expression contributes to the development of diabetic coronary microvascular dysfunction, and provide compelling support for eNAMPT inhibition as a novel and effective therapeutic strategy for CMD in diabetes.

Insulin resistance-related circulating predictive markers in the metabolic syndrome: a systematic review in the Iranian population.

Background: Specific biomarkers for metabolic syndrome (MetS) may improve diagnostic specificity for clinical information. One of the main pathophysiological mechanisms of MetS is insulin resistance (IR). This systematic review aimed to summarize IR-related biomarkers that predict MetS and have been investigated in Iranian populations. Methods: An electronic literature search was done using the PubMed and Scopus databases up to June 2022. The risk of bias was assessed for the selected articles using the instrument suggested by the Joanna Briggs Institute (JBI). This systematic review protocol was registered with PROSPERO (registration number CRD42022372415). Results: Among the reviewed articles, 46 studies investigated the association between IR biomarkers and MetS in the Iranian population. The selected studies were published between 2009 and 2022, with the majority being conducted on adults and seven on children and adolescents. The adult treatment panel III (ATP III) was the most commonly used criteria to define MetS. At least four studies were conducted for each IR biomarker, with LDL-C being the most frequently evaluated biomarker. Some studies have assessed the diagnostic potency of markers using the area under the curve (AUC) with sensitivity, specificity, and an optimal cut-off value. Among the reported values, lipid ratios and the difference between non-HDL-C and LDL-C levels showed the highest AUCs (≥ 0.80) for predicting MetS. Conclusions: Considering the findings of the reviewed studies, fasting insulin, HOMA-IR, leptin, HbA1c, and visfatin levels were positively associated with MetS, whereas adiponectin and ghrelin levels were negatively correlated with this syndrome. Among the investigated IR biomarkers, the association between adiponectin levels and components of MetS was well established. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01347-6.

Visfatin impact on the proteome of porcine luteal cells during implantation.

Visfatin (VIS) is a hormone belonging to the adipokines' group secreted mainly by the adipose tissue. VIS plays a crucial role in the control of energy homeostasis, inflammation, cell differentiation, and angiogenesis. VIS expression was confirmed in the hypothalamic-pituitary-gonadal (HPG) axis structures, as well as in the uterus, placenta, and conceptuses. We hypothesised that VIS may affect the abundance of proteins involved in the regulation of key processes occurring in the corpus luteum (CL) during the implantation process in pigs. In the present study, we performed the high-throughput proteomic analysis (liquid chromatography with tandem mass spectrometry, LC-MS/MS) to examine the in vitro influence of VIS (100 ng/mL) on differentially regulated proteins (DRPs) in the porcine luteal cells (LCs) on days 15-16 of pregnancy (implantation period). We have identified 511 DRPs, 276 of them were up-regulated, and 235 down-regulated in the presence of VIS. Revealed DRPs were assigned to 162 gene ontology terms. Western blot analysis of five chosen DRPs, ADAM metallopeptidase with thrombospondin type 1 motif 1 (ADAMTS1), lanosterol 14-α demethylase (CYP51A1), inhibin subunit beta A (INHBA), notch receptor 3 (NOTCH3), and prostaglandin E synthase 2 (mPGES2) confirmed the veracity and accuracy of LC-MS/MS method. We indicated that VIS modulates the expression of proteins connected with the regulation of lipogenesis and cholesterologenesis, and, in consequence, may be involved in the synthesis of steroid hormones, as well as prostaglandins' metabolism. Moreover, we revealed that VIS affects the abundance of protein associated with ovarian cell proliferation, differentiation, and apoptosis, as well as CL new vessel formation and tissue remodelling. Our results suggest important roles for VIS in the regulation of ovarian functions during the peri-implantation period.

Effect of non-surgical periodontal therapy on salivary and gingival crevicular fluid concentration of visfatin in periodontal health and disease.

Background and objective: Visfatin, a pleotropic mediator mostly produced by visceral fat, is crucial in controlling the immunological and defensive systems. It serves the roles of a cytokine, an enzyme involved in energy metabolism, and a growth factor. The objective of the present study was to assess the impact of non-surgical periodontal therapy (scaling and root planing) on visfatin concentrations in saliva and gingival crevicular fluid in individuals with Periodontitis (stage-II grade-A). Materials and methods: 54 individuals were divided into Group A (Periodontally Healthy) and Group B1(Periodontitis baseline) based on periodontal parameters including plaque index (PI), gingival index (GI), probing pocket depth (PPD), clinical attachment level (CAL), and radiographic parameters. After NSPT (SRP), Group B1 patients were recalled after 4 weeks, constituting Group B2 (post NSPT group B1). At baseline and 4 weeks after non-surgical periodontal therapy (SRP), all clinical parameters, salivary and GCF samples were recorded. An ELISA kit was used to measure the levels of visfatin. Using the paired t-test, unpaired t-test, and Pearson's correlation coefficient, data were analysed using SPSS 15. Results: After non-surgical periodontal treatment (SRP), the mean salivary and gingival crevicular fluid concentration of visfatin considerably decreased to a level comparable to periodontal health. In all groups, GCF visfatin concentration was higher than salivary concentration of visfatin. In periodontitis patients, visfatin concentration in GCF was 1.5 times higher than in saliva. Conclusion: The results of this investigation suggest a direct correlation between salivary and gingival crevicular fluid visfatin concentration and periodontal tissue inflammation and disease activity.

Status of visfatin in female reproductive function under normal and pathological conditions: a mini review.

Adipokines are now well-known to regulate reproduction. Visfatin is an adipokine expressed in the hypothalamus, pituitary, ovary, uterus, and placenta of different species, and since it has been found to modulate the endocrine secretion of the hypothalamus, pituitary gland and ovary, it may be considered a novel regulator of female reproduction. Although the majority of the literature explored its role in ovarian regulation, visfatin has also been shown to regulate uterine remodeling, endometrial receptivity and embryo development, and its expression in the uterus is steroid dependent. Like other adipokines, visfatin expression and levels are deregulated in pathological conditions including polycystic ovary syndrome. Thus, the present mini-review focuses on the role of visfatin in female reproduction under both physiological and pathological conditions.

The interplay between extracellular NAMPT and inflammatory cytokines in preeclampsia.

Preeclampsia (PE) is the major cause of maternal-fetal mortality and morbidity. Its pathophysiology is not elucidated, but there is evidence for the role of visfatin/nicotinamide phosphoribosyl transferase (NAMPT), mainly due to its relation to endothelial dysfunction, a hallmark of PE. However, there is heterogeneous data regarding visfatin/NAMPT in healthy pregnancy (HP) and PE. Therefore, we performed a search on MEDLINE/PubMed using the terms "visfatin and preeclampsia" and "NAMPT and preeclampsia, and we selected 23 original articles: 12 articles reported increased levels in PE compared to HP, only four articles showed lower levels and eight articles did not find differences regarding visfatin/NAMPT in the groups studied. It is widely acknowledged that levels detected in plasma, serum, or placenta can be influenced by the size of the population and sample analyzed, as well as genetic factors. We further discussed the correlations of visfatin/NAMPT with clinical biomarkers in PE and inflammatory pathways. Considering the common inflammatory mechanisms between PE and visfatin/NAMPT, few studies have recently performed serum or plasma dosages. In conclusion, further studies are needed to highlight the potential role of visfatin/NAMPT in the pathophysiology of PE. This will provide comparative evidence to establish it as a biomarker for disease outcomes and treatment.

An oncolytic HSV-1 armed with Visfatin enhances antitumor effects by remodeling tumor microenvironment against murine pancreatic cancer.

Oncolytic viruses (OVs) have shown potential in converting a "cold" tumor into a "hot" one and exhibit effectiveness in various cancer types. However, only a subset of patients respond to oncolytic virotherapy. It is important to understand the resistance mechanisms to OV treatment in pancreatic ductal adenocarcinoma (PDAC) to engineer oncolytic viruses. In this study, we used transcriptome RNA sequencing (RNA-seq) to identify Visfatin, which was highly expressed in the responsive tumors following OV treatment. To explore the antitumor efficacy, we modified OV-mVisfatin, which effectively inhibited tumor growth. For the first time, we revealed that Visfatin promoted the antitumor efficacy of OV by remodeling the tumor microenvironment, which involved enhancing CD8+ T cell and DC cell infiltration and activation, repolarizing macrophages towards the M1-like phenotype, and decreasing Treg cells using single-cell RNA sequencing (scRNA-seq) and flow cytometry. Furthermore, PD-1 blockade significantly enhanced OV-mVisfatin antitumor efficacy, offering a promising new therapeutic strategy for PDAC.

Expression of visfatin in gingival crevicular fluid and gingival tissues in different periodontal conditions: a cross-sectional study.

BACKGROUND: Studies have shown that visfatin is an inflammatory factor closely related to periodontitis. We examined the levels of visfatin in gingival crevicular fluid (GCF) and gingival tissues under different periodontal conditions, in order to provide more theoretical basis for exploring the role of visfatin in the pathogenesis of periodontitis. METHODS: We enrolled 87 subjects, with 43 in the chronic periodontitis (CP) group, 21 in the chronic gingivitis (CG) group, and 23 in the periodontal health (PH) group. Periodontal indexes (PD, AL, PLI, and BI) were recorded. GCF samples were collected for visfatin quantification, and gingival tissues were assessed via immunohistochemical staining. RESULTS: Visfatin levels in GCF decreased sequentially from CP to CG and PH groups, with statistically significant differences (P < 0.05). The CP group exhibited the highest visfatin levels, while the PH group had the lowest. Gingival tissues showed a similar trend, with significant differences between groups (P < 0.001). Periodontal indexes were positively correlated with visfatin levels in both GCF and gingival tissues (P < 0.001). A strong positive correlation was observed between visfatin levels in GCF and gingival tissues (rs = 0.772, P < 0.001). CONCLUSION: Greater periodontal destruction corresponded to higher visfatin levels in GCF and gingival tissues, indicating their potential collaboration in damaging periodontal tissues. Visfatin emerges as a promising biomarker for periodontitis and may play a role in its pathogenesis.

Comparative expression and localization of visfatin, chemerin, and chemerin receptor proteins in a heat-stressed mouse testis.

The adipokines, visfatin, chemerin, and its receptor are expressed in the testis. It has also been shown that heat-stress alters the secretion and expression of other adipokines. Testicular heat-stress is now well known to cause the impairment in the testis. It has also been documented that heat-stress changes the expression of genes and proteins in the testis. To the best of our knowledge, the expression and localization of visfatin chemerin and its receptor have not been investigated in the heat-stressed testis. Therefore, the present study has investigated the expression and localization of these proteins in the heat-stressed testis. The expression of visfatin and chemerin and receptor exhibits a differential repossess against the heat stress. Visfatin expression was up-regulated while chemerin and chemerin receptor was down-regulated in the heat-stressed testis as shown by western blot analysis. The immunolocalization of visfatin and chemerin showed increased abundance in the seminiferous tubules of heat-stressed mice testis. Furthermore, abundance of visfatin, chemerin, and its receptor showed a decrease in abundance in the Leydig cells of heat-stressed testis. The decreased abundance of these proteins in the Leydig cells coincides with decreased 3ß-HSD immunostaining along with decreased testosterone levels. These results suggest that heat-stress might decrease testosterone secretion by modulating visfatin and chemerin in the Leydig cells. The increased abundance of visfatin and chemerin in the primary spermatocytes, round spermatid, and multinucleated germ cells also coincides with increased immunostaining of active caspase-3. Moreover, expression of Bcl-2 was down-regulated, and expression of active caspase-3 and HSP70 were up-regulated along with increased oxidative stress in the heat-stressed testis, suggesting stimulated apoptosis. In conclusion, our results showed that visfatin, chemerin, and its receptor are differentially expressed in the testis under heat-stress and within the testis also it might differentially regulate testosterone biosynthesis in the Leydig cells and apoptosis in the seminiferous tubules.

Association between visfatin and periodontitis: a systematic review and meta-analysis.

Background: Periodontitis is a chronic inflammatory disease caused by bacterial infection in the periodontal support tissue. Visfatin, a hormone secreted mainly by adipocytes and macrophages, plays an important role in immune regulation and defense. Although studies have indicated that patients with periodontitis have significantly high serum and gingival crevicular fluid levels of visfatin, the relationship between this adipocytokine and periodontal disease remains unclear. Aim: The aim of this study was to systematically evaluate the association between visfatin levels and periodontitis. Methods: The PubMed, Web of Science, ScienceDirect, EBSCO, and Wiley Online Library databases were searched for potential studies, using "periodontitis" and "visfatin" as the keywords in the title and abstract search fields. Standardized mean difference (SMD) values with corresponding 95% confidence intervals (CIs) were determined from the results of this meta-analysis. Results: In total, 22 articles involving 456 patients with periodontitis and 394 healthy individuals (controls) were included in the meta-analysis. Visfatin levels were significantly higher in the patients with periodontitis than in the healthy individuals (SMD: 3.82, 95% CI [3.01-4.63]). Moreover, the visfatin levels were significantly lowered after periodontitis treatment (SMD: -2.29, 95% CI [-3.33 to -1.26]). Conclusion: This first-ever meta-analysis comparing visfatin levels between patients with periodontitis and healthy individuals suggests that this adipocytokine can be a diagnostic and therapeutic biomarker for periodontal disease.

Unlocking the Dietary Puzzle: How Macronutrient Intake Shapes the Relationship between Visfatin and Atherosclerosis in Type 2 Diabetes.

Background and Objectives. Optimal nutrition for type 2 diabetes (T2DM) aims to improve glycemic control by promoting weight loss and reducing adipose tissue, consequently improving cardiovascular health. Dietary alterations can influence adipose tissue metabolism and potentially impact adipocytokines like visfatin, thereby affecting atherosclerosis development. This study aimed to investigate dietary habits and adherence to recommendations among individuals with T2DM and to examine how dietary adherence influences the association between visfatin and subclinical atherosclerosis. Materials and Methods: This cross-sectional multicenter study involved 216 adults (30-70 years) with T2DM, assessing dietary habits, adherence to recommendations (carbohydrates, fats, protein, fiber, saturated fatty acid, polyunsaturated and monounsaturated fatty acid (PUFA and MUFA) and salt), and the association between visfatin and subclinical atherosclerosis. Participants completed 24 h dietary recalls; dietary misreporting was assessed using the Goldberg cut-off method. Carotid intima-media thickness (IMT) and plaque occurrence were evaluated with ultrasound, while visfatin levels were measured using Luminex's xMAP technology. Results: Three of the eight recommendations were followed in 31% of subjects, two in 26%, and four in 20%, with the highest adherence to MUFA and protein intake. Significant correlations between IMT and visfatin were observed in individuals with specific dietary patterns. The association between IMT and visfatin persisted when PUFA and MUFA intake aligned with recommendations. PUFA intake ≤ 10% and MUFA ≤ 20% of total energy significantly correlated with carotid artery IMT (p = 0.010 and p = 0.006, respectively). Visfatin's associations with IMT remained significant (p = 0.006) after adjusting for common risk factors, medication use, and dietary nonadherence. No association was observed with carotid artery plaque. Conclusions: Dietary compliance was limited, as only 31% adhered even to three of eight recommendations. A common dietary pattern characterized by low carbohydrate and fiber but high fat, total fat, saturated fat, and salt intake was identified. This pattern amplifies the statistical association between visfatin and subclinical atherosclerosis.

Maternal Blood Adipokines and Their Association with Fetal Growth: A Meta-Analysis of the Current Literature.

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines.

The role of adipokines in osteoporosis management: a mini review.

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.

Relationship between serum apelin, visfatin levels, and body composition in Polycystic Ovary Syndrome patients.

OBJECTIVE: To investigate the relationship between body composition and serum visfatin and apelin levels in patients with polycystic ovary syndrome (PCOS). METHODS: In this prospective observational study, the differences in body composition, levels of gonadal hormone concentrations, glucose metabolism, apelin, and visfatin were compared between PCOS patients and the control group. PCOS patients were further divided into different subgroups according to different obesity criteria and the differences between serum visfatin and apelin levels in different subgroups were compared. Finally, the correlation of serum visfatin levels and apelin levels with body composition, and metabolism-related indicators in PCOS patients was explored. RESULTS: A total collected 178 cases of PCOS patients and 172 cases of healthy women (control group) between 2020 July and 2021 November. In PCOS patients, their weight, Body Mass Index (BMI), Waist Hip Rate (WHR), Fat-Free Mass Index (FFMI), Percent Body Fat (PBF), Fat mass index (FMI), PBF of Arm, PBF of Leg, PBF of the Trunk, Visceral Fat Level (VFL), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Luteinizing hormone (LH) were significantly higher than in the control group (all P < 0.001), Percent Skeletal Muscle (PSM), PSM of Leg, and PSM of the Trunk were significantly decreased than in the control group (all P < 0.001). The PCOS patients had significantly higher serum visfatin levels and apelin levels compared with the control group (all P < 0.001). In PBF > 35 % PCOS patients, the apelin and visfatin levels were significantly higher than the PBF ≤ 35 % PCOS patients. In WHR ≥ 0.85 and BMI ≥ 24 kg/m2 PCOS patients, the visfatin levels were significantly higher than the WHR < 0.85 and BMI < 24 kg/m2 PCOS patients. Serum apelin and visfatin positively correlated with BMI level, WHR, FFMI, PBF, FMI, PBF of arms, PBF of legs, PBF of the trunk, VFL, FBG, HOMA-IR index and negatively correlated with PSM, PSM of legs, and PSM of the trunk (all P < 0.001). CONCLUSIONS: Compared with healthy women, Patients with PCOS have an increased fat content in various parts of the body, reduced skeletal muscle content, and are often complicated by metabolic abnormalities. Serum visfatin and apelin correlated not only with obesity, fat mass, and fat distribution but also with muscle mass and distribution. It may be possible to reduce the long-term risk of metabolic disease in PCOS through the monitoring and management of the body composition in PCOS patients or to reflect the therapeutic effect of PCOS.

Role of the intracerebroventricular injection of the visfatin and its interaction with neuropeptide Y and nitric systems on food intake in neonatal chicken.

Visfatin play an essential role in the central regulation of appetite in birds. This study aimed to determine role of intracerebroventricular (ICV) injection of the visfatin on food intake and its possible interaction with neuropeptide Y (NPY) and nitric oxide system in neonatal broiler chicken. In experiment 1, neonatal chicken received ICV injection visfatin (1, 2 and 4 µg). In experiment 2, chicken received ICV injection of B5063 (NPY1 receptor antagonist 1.25 µg), visfatin (4 µg) and co-injection of the B5063 + Visfatin. In experiments 3-6, SF22 (NPY2 receptor antagonist 1.25 µg), SML0891 (NPY5 receptor antagonist 1.25 µg), L-NAME (nitric oxide synthase inhibitor, 100 nmol) and L-arginine (Precursor of nitric oxide, 200 nmol) were injected instead of B5063. Then the amount of cumulative food was measured at 30, 60 and 120 min after injection. Obtained data showed, injection visfatin (2 and 4 µg) increased food intake compared to control group (P < 0.05). Co-injection of the B5063 + Visfatin decreased visfatin-induced hyperphagia compared to control group (P < 0.05). Co-injection of the L-NAME + Visfatin amplified visfatin-induced hyperphagia compared to control group (P < 0.05). The result showed that visfatin has hyperphagic role and this effect mediates via NPY1 and nitric oxide system in neonatal chicken.

Adiponectin and visfatin expression profile in extra-embryonic annexes and role during embryo development in layer and broiler chickens.

Some evidence showed differences between layer and broiler embryo development. We recently showed that two adipokines, adiponectin and visfatin are expressed in the extra embryonic membranes and fluids. However, their role in the embryo development is unknown. Thus, our objectives were 1. to compare the expression of AdipoQ and its receptors AdipoR1 and AdipoR2 and visfatin in extra-embryonic annexes in broiler and layer breeders during the embryo development and 2. to investigate the role of two adipokines in embryo development in both broiler and layer breed after in ovo injection of blocking antibodies against chicken adiponectin or visfatin. We found that adiponectin, AdipoR1, AdipoR2 and visfatin were mainly more expressed in the allantoic that in amniotic membranes. In addition, these expressions increased according the stage of embryo development. We observed a higher expression in layer than in broiler of AdipoQ in allantoic membranes at ED14 and ED18, of AdipoR1 and AdipoR2 in both allantoic and amniotic membranes at ED7 and ED14 and of visfatin only in allantoic membrane from ED7 to ED18. AdipoQ and visfatin were absent in amniotic fluid at ED7 but present at ED14 or ED18 where higher concentrations were detected in layer than in broiler. Interestingly, we showed a strong positive correlation between Adipo and visfatin concentration in amniotic fluid and the body weight of embryo in both breeds. However, after in ovo injection of Adipo antibodies we did not observe any effect on the embryo mortality whereas injection of visfatin antibodies increased in a dose dependent manner the embryo mortality in both breeds. Taken together, Adipo and visfatin are higher expressed in layer than broiler in extra-embryonic membranes and amniotic fluid. Our data suggest also that visfatin could be a main regulator of embryo development.

Differential effect of visfatin inhibition on the testicular androgen and estrogen receptors expression in early pubertal mice.

BACKGROUND: It is now well known that visfatin is expressed in the testis and ovary of various animals. Visfatin is known to regulate gonadal functions such as steroidogenesis, proliferation, and apoptosis in the ovary and testis of mice. Recently, we have shown that visfatin has an inhibitory role in the infantile mice testis. It has also been shown that visfatin stimulates testicular steroidogenesis in adult rats. However, the role of visfatin during puberty has not been investigated in relation to the above-mentioned process. OBJECTIVE: The objective of the present study was to examine the effect of visfatin inhibition by FK866 from PND25 to PND35 (pre-pubertal to early pubertal) in male Swiss albino mice on steroidogenesis, proliferation, and apoptosis. METHODS: Sixteen mice (25 days old) were divided into two groups, one group was given normal saline and the other group was administered with an inhibitor of visfatin (FK866) at the dose of 1.5 mg/kg by intraperitoneal injection for 10 days. Histopathological and immunohistochemical analysis, western blot analysis and hormonal assay were done. RESULTS: Visfatin inhibition resulted in increased estrogen secretion, body weight, seminiferous tubule diameter, germinal epithelium height, and proliferation along with increased expression of BCl2, casapse3, ERs and aromatase expression in the mice testis. Visfatin inhibition down-regulated the testicular visfatin expression and also decreased abundance in the adipose tissues. CONCLUSION: In conclusion, decreased AR expression and increased ERs expression by FK866, suggest that visfatin might have a stimulatory effect on AR signaling than ERs in the early pubertal stage of mice.

Increased serum visfatin level is associated with fat deposition of the lumbar spine in ankylosing spondylitis patients.

Objectives: To assess the serum visfatin levels in patients with ankylosing spondylitis (AS), as well as its correlation with fat deposition of the lumbar spine. Methods: Serum visfatin levels were detected by enzyme-linked immunosorbent assay (ELISA) in 50 AS patients and 75 sex-and age-matched healthy controls. The clinical and laboratory indexes of AS patients were recorded, and the lumbar spine magnetic resonance scan was performed to evaluate the lumbar spine fat deposition in AS patients. The level of serum visfatin and its correlation with lumbar fat deposition were analyzed, and the risk factors of AS lumbar MRI fat deposition were evaluated by Logistic regression. Results: Serum visfatin levels in AS patients were elevated compared with that in healthy controls (p < 0.001), and were more significant in patients with fat deposition and syndesmophyte formation (p = 0.017 and p = 0.014, respectively). Serum visfatin levels were positively correlated with CRP, BASDAI, mSASSS and fat deposition (all p < 0.05). Age (OR = 1.085, 95% CI: 1.005-1.173, p = 0.038), disease duration (OR = 1.267, 95% CI: 1.017-1.578, p = 0.035), and visfatin (OR = 1.846, 95% CI: 1.004-3.393, p = 0.048) were risk factors for fat deposition in AS patients. Conclusions: The level of serum visfatin in AS patients is significantly increased, which is associated with fat deposition on lumbar MRI. Elevated visfatin level is an independent risk factor for AS lumbar fat deposition.

Effect of Fibrate Treatment on Circulating Adipokine Levels: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear. AIM OF THE STUDY: This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels. METHODS: Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method. RESULTS: This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: -1.58 ng/mL, 95% CI: -2.96, -0.20, p = 0.02, I2 = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: -13.86 ng/mL, 95% CI: -26.70, -1.03, p = 0.03, I2 = 99%), and visfatin (WMD: -1.52 ng/mL, 95% CI: -2.49, -0.56, p = 0.002, I2 = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: -0.69 µg/ml, 95% CI: -1.40, 0.02, p = 0.06, I2 = 83%) and resistin (WMD: -2.27 ng/mL, 95% CI: -7.11, 2.57, p = 0.36, I2 = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1. CONCLUSION: This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.