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.

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.

Evaluation of Serum Adipokine Levels in Girls With Central Precocious Puberty.

PURPOSE: Adipose tissue has an important endocrine function by secreting a variety of hormones known as adipokines, such as Visfatin, Omentin-1 and Chemerin. On the other hand, these hormones are also secreted from places other than fatty tissues in the girl's genital system. The goal of this study was to demonstrate the secretory status of adipokines in patients with central precocious puberty (CPP) and their utility in the diagnosis of precocious puberty. METHOD: A total of 105 patients were included in the study (53 in the CPP group and 52 in the control group). The following were used as the CPP diagnostic criteria; breast development, basal LH measurement higher than 0.3 IU/L, peak LH level ≥ 5 IU/L, peak LH/FSH ratio ≥ 0.66 (after 0.1 mg GnRH stimulation test) and a difference of at least 1 year between bone and chronological age. RESULTS: A statistically significant difference was detected between the groups in serum Omentin-1 and Chemerin levels, and no significant differences were detected between the groups in Visfatin values. The cut-off values for the diagnosis of CPP were calculated as ≤ 48.9 with 81% sensitivity and 54% specificity for Omentin-1, and as ≥ 417 with 85% sensitivity and 60% specificity for Chemerin. CONCLUSION: In our study, we found that Omentin-1 level decreased and Chemerin level increased in lean girls with CPP. More studies are needed to elucidate how adipokines play roles in explaining the onset of CPP, and whether they may be used as a reliable marker for the diagnosis of CPP.

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.

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.

Bariatric Surgery in Obesity: Metabolic Quality Analysis and Comparison of Surgical Options.

Obesity is a constantly growing health problem which reduces quality of life and life expectancy. Bariatric surgery (BS) for obesity is considered when all other conservative treatment modalities have failed. Comparison of the multidisciplinary programs with BS regarding to the weight loss showed that substantial and durable weight reduction have been achieved only with bariatric surgical treatments. Although laparoscopic sleeve gastrectomy is the most popular BS, it has high long-term failure rates, and it is claimed that one of every three patients will undergo another bariatric procedure within a 10-year period. Although BS provides weight loss and improvement of metabolic comorbidities, in long-term follow-up, weight gain is observed in half of the patients, while decrease in bone mass and nutritional deficiencies occur in up to 90%. Moreover, despite significant weight loss, several psychological aspects of patients are worsened in comparison to preoperative levels. Nearly one-fifth of postoperative patients with "Loss-of-eating control" meet food addiction criteria. Therefore, the benefits of weight loss following bariatric procedures alone are still debated in terms of the proinflammatory and metabolic profile of obesity.

Effect of non-surgical periodontal treatment on visfatin and chemerin concentration in the gingival crevicular fluid.

Visfatin, as a novel adipokine, is considered to play a role in periodontal inflammation. Chemerin is another newly identified adipokine that is possible to have a role in periodontitis firstly reported in our previous study. The aim of the current study is to evaluate the gingival crevicular fluid (GCF) levels of visfatin and chemerin in periodontitis and and compare these adipokine levels with before and after non-surgical periodontal treatment. Twenty-nine patients with Stage III Grade B periodontitis and eighteen healthy subjects included in this cross-sectional cohort study. Clinical periodontal parameters and GCF were obtained from all subjects. Eight weeks after the following non-surgical periodontal treatment including scaling and root planning, samples and clinical periodontal parameters were collected again in the periodontitis group. The levels of adipokines were analyzed with standard enzyme-linked immunosorbent assay. The levels of visfatin and chemerin were statistically significantly higher at periodontitis group as compared to healthy group (P < 0.001). Although, no changes were observed in visfatin levels after periodontal treatment (P > 0.05), chemerin levels were significantly decreased (P < 0.001). Also, no differences were observed as compared to the healthy group (P > 0.05). Visfatin and chemerin may play a role in the periodontal disease process. In addition, it can be considered that the decreased chemerin levels after non-surgical periodontal treatment may play an important role for developing host modulation strategies.

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.

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.

Visfatin aggravates transverse aortic constriction-induced cardiac remodelling by enhancing macrophage-mediated oxidative stress in mice.

Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.

Retinol-Binding Protein 4 and Visfatin Levels in Patients with Periodontitis and Obesity/Overweight: A Systematic Review and Meta-Analysis.

Prior studies demonstrated an equivocal conclusion about the association between the level of retinol-binding protein 4 (RBP4)/visfatin and periodontitis patients with obesity. The aim of our study (Prospero ID: CRD42023469058) was to systematically review the available articles linking the biofluid levels of RBP4/visfatin to the comorbidity of periodontitis and obesity. Clinical trials were screened in accordance with specific inclusion criteria from seven databases up to November 2023. A quality assessment was performed with the Newcastle-Ottawa Scale and ROBINS-I tools for observational and interventional trials, respectively. The standard mean difference (SMD) with a 95% confidence interval (CI) related to the RBP4 level was recorded; the other indicators related to the visfatin level were measured via the mean difference (MD) with the corresponding 95% CI, and Fisher's Z transformation was measured to reveal the association using Review Manager 5.4. The current evidence was based on five observational studies and two interventional studies. All of them were included in the systematic review, and six of them were in the meta-analysis. Statistical analysis indicated that there was no significant difference in the circulating levels of RBP4 in the periodontitis patients with obesity or without, who were labeled as OP or NP, respectively (155 OP-107 NP: SMD = 1.38; 95% CI: -0.18-2.94, p = 0.08), as well as the periodontal healthy patients with a normal weight, who were labelled as NnP (116 OP-79 NnP: SMD = 6.76; 95% CI: -5.34-18.87, p = 0.27). Meanwhile, a significant higher level of serum visfatin was found in the OP patients than that of the NP (86 OP-45 NP: MD = 4.21; 95% CI: 2.65-5.77, p < 0.00001)/NnP (164 OP-88 NnP: MD = 13.02; 95% CI: 7.34-18.70, p < 0.00001) group. In addition, a positive association was observed between the serum RBP4 and body mass index/clinical attachment loss (CAL). And, then, there was a positive association between the serum visfatin and periodontal parameters, including the probing depth, CAL, and plaque index, as well as metabolic parameters, including the total cholesterol, triglycerides, fasting blood glucose, and low-density lipoprotein cholesterol. Here, the circulating RBP4 level was not independently related to the comorbidity of periodontitis and obesity, while serum visfatin was significantly associated with periodontitis and obesity. Notably, the positive association between circulating RBP4/visfatin and the periodontal parameters/metabolic parameters firmly suggested that the higher severity of the obese or periodontal status was associated with an elevated level of serum visfatin or RBP4 in the OP group. With more rigorous longitudinal research, the exact causations between RBP4/visfatin and the patients affected by obesity and periodontitis could be disentangled. RBP4 and visfatin might be novel, enlightening prospective bio-indexes for the targeted treatment of comorbidities.

Adipokines and epithelial-mesenchymal transition (EMT) in cancer.

Obesity is a significant risk factor for cancer development. Within the tumor microenvironment, adipocytes interact with cancer cells, immune cells, fibroblasts and endothelial cells, and orchestrate several signaling pathways by secreting bioactive molecules, including adipokines. Adipokines or adipocytokines are produced predominantly by adipocytes and function as autocrine, paracrine and endocrine mediators. Adipokines can exert pro- and anti-inflammatory functions, and they play a pivotal role in the state of chronic low-grade inflammation that characterizes obesity. Epithelial-mesenchymal transition (EMT), a complex biological process whereby epithelial cells acquire the invasive, migratory mesenchymal phenotype is well-known to be implicated in cancer progression and metastasis. Emerging evidence suggests that there is a link between adipokines and EMT. This may contribute to the correlation that has been documented between obesity and cancer progression. This review summarizes the existing body of evidence supporting an association between the process of EMT in cancer and the adipokines leptin, adiponectin, resistin, visfatin/NAMPT, lipocalin-2/NGAL, as well as other newly discovered adipokines including chemerin, nesfatin-1/nucleobindin-2, AZGP1, SFRP5 and FABP4.

Role of adipokines (omentin and visfatin) in coronary artery disease.

AIMS: Adipose tissue is considered as an endocrine organ that releases bioactive factors known as adipokines which contribute to the pathogenesis of rotundity-linked metabolic and cardiovascular complications. Rotundity is a major predisposer for the development and progression of coronary artery disease (CAD). DATA SYNTHESIS: The literature survey from various databases such as Pubmed/Medline, DOAJ, Scopus, Clarivate analytics/Web of Science and Google Scholar were used to prepare this article. The epidemic of rotundity has gained significant attention to understand the biology of adipocytes and the metabolism of adipose tissue in obese individuals. In CAD, visfatin/NAMPT was primarily indicated as a clinical marker of atherosclerosis, endothelial dysfunction and vascular injury having a prognostic significance. Visfatin/NAMPT is a factor that promotes vascular inflammation and atherosclerosis. Omentin is an anti-inflammatory and anti-atherogenic adipokine regulating cardiovascular functions. CONCLUSIONS: This review highlights and summarizes the scientific information pertaining to the role of the adipokines - omentin and visfatin in CAD.

Evaluation of serum adipokines (omentin-1 and visfatin) in coronary artery disease at a North Indian hospital.

Objective. Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated. Methods. In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded. Results. The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p<0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p<0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group. Conclusion. The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.

Plasma visfatin and apelin levels in adolescents with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that usually begins during adolescence. Patients may have severe metabolic disorders. OBJECTIVE: To investigate the levels of visfatin and apelin in adolescent girls with PCOS and to explore the importance of visfatin and apelin in glucose and lipid metabolism. METHODS: A total of 88 girls (aged 12-20 years) were prospectively and consecutively recruited during two years for the PCOS group (n = 44) and the control group (n = 44). Serum visfatin, apelin and other metabolic parameters were measured. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: Visfatin, apelin and indicators of glucose and lipid-metabolism were not different for PCOS patients compared to control. However, insulin resistance (IR) in the PCOS-group was more frequent (p < 0.05). Visfatin in non-IR patients was higher than in IR-patients in the PCOS-group (p < 0.05). However, there was no difference in apelin levels between IR and non-IR patients in the PCOS-group (p > 0.05). ROC-curve analyses demonstrated that the optimal value of visfatin for predicting IR in PCOS-patients was 7.14 ng/mL, with 78.1% sensitivity and 68.7% specificity. In the PCOS-group, visfatin was positively correlated with high density lipoprotein cholesterol (HDL-C), and negatively correlated with HOMA-IR, apolipoprotein B (Apo-B), cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and CHO/HDL-C ratio (p < 0.05). Apelin had no correlation with all indices (p > 0.05). CONCLUSIONS: Higher visfatin levels may prevent IR in adolescent PCOS patients, showing a positive predictive value for IR and also reflecting a beneficial effect on lipids. It is a possible protective factor at certain stages of metabolic syndrome.

Hormonal regulation of visfatin and adiponectin system in quail muscle cells.

Visfatin and adiponectin are two adipokines known to regulate energy homeostasis and stress response within different peripheral tissues. Their role and regulation in highly metabolically active tissue such as the muscle is of particular interest. As modern poultry exhibit insulin resistance, obesity, and hyperglycemia along with a lack of insight into the regulation of these avian adipokines, we undertook the present work to determine the regulation of visfatin and adiponectin system by cytokines and obesity-related hormones in a relevant in vitro model of avian muscle, quail muscle (QM7) cells. Cells were treated with pro-inflammatory cytokine IL-6 (5 and 10 ng/mL) and TNFα (5 and 10 ng/mL), as well as leptin (10 and 100 ng/mL) and both orexin-A and orexin-B (ORX-A/B) (5 and 10 ng/mL). Results showed significant increases in visfatin mRNA abundance under both cytokines (IL-6 and TNFα), and down regulation with ORX-B treatment. Adiponectin expression was also upregulated by pro-inflammatory cytokines (IL-6 and TNFα), but down regulated by leptin, ORX-A, and ORXB. High doses of IL-6 and TNFα up regulated the expression of adiponectin receptors AdipoR1 and AdipoR2, respectively. Leptin and orexin treatments also down regulated both AdipoR1 and AdipoR2 expression. Taken together, this is the first report showing a direct response of visfatin and the adiponectin system to pro-inflammatory and obesity-related hormones in avian muscle cells.

Association analysis of indels in the VISFATIN gene with five cattle breeds and their growth traits.

VISFATIN is an adipose cytokine that has been proved to correlate with growth and development traits. In a previous study from our lab, two insertion/deletions (indels; including a 35-bp insertion at its intron 4 and a 6-bp deletion in intron 5) were identified within the VISFATIN gene. To validate these indels and evaluate their association with growth traits in Chinese cattle, a total of 413 samples from four Chinese indigenous breeds and 217 samples from Chinese breeds were detected. Three genotypes (WW, WI and II) at intron 4 were detected based on the 35-bp insertion (allele I) or deletion (allele W) and showed moderate polymorphism in all samples. Two genotypes (WW and WD) at intron 5 were detected based on the 6-bp deletion (allele D) or insertion (allele W) in Xianan (XN) cattle and Jinnan (JN) cattle population but showed poor polymorphisms. Association analysis illustrated that the indel at intron 4 is significantly associated with chest girth, rump length and body weight in Ji'an (JA) cattle and the indel at intron 5 can cause a significant difference in rump length in JN cattle. To our knowledge, it is the first time it has been shown that indels within the VISFATIN gene are associated with growth traits in the two Chinese indigenous cattle breeds. These findings suggest that the VISFATIN gene can be used as a molecular marker for JN and JA cattle breeding.

Evaluation of the adipokine levels of pregnant women with preeclampsia.

AIM: The aim of this study was to compare maternal blood and umbilical-cord leptin, spexin and visfatin levels during delivery in severe preeclampsia (PE) with controls, and to evaluate whether any clinical or demographic variables had independent associations with them. METHODS: This is a case-controlled observational study consisting of 45 pregnant women with severe PE and a control group consisting of gestational age-matched 45 healthy pregnant women. We examined the leptin, spexin, and visfatin levels in serum samples taken from maternal blood and umbilical cords during cesarean section in both groups. Leptin, spexin, and visfatin levels were measured by enzyme-linked immunosorbent assay. RESULTS: The maternal leptin and visfatin levels were significantly higher and the maternal spexin levels were significantly lower in the PE group than in the control group (p < 0.001). Similar to the maternal adipokine levels, the umbilical-cord leptin and visfatin levels were significantly higher and the spexin levels were significantly lower in the PE group (p < 0.001). We found a significant positive correlation between maternal body mass index and maternal blood and umbilical-cord serum leptin and visfatin levels in both groups (p < 0.001). CONCLUSION: The leptin, spexin and visfatin levels were significantly altered in the nondiabetic preeclamptic women in our study. We believe that the main reason for these changes may be the hypoxic placenta to protect the fetus and maintain its nutrition.

Changes in the Subchondral Bone, Visfatin, and Cartilage Biomarkers after Pharmacological Treatment of Experimental Osteoarthritis with Metformin and Alendronate.

Subchondral bone that has intense communication with the articular cartilage might be a potential target for pharmacological treatment in the early stages of osteoarthritis (OA). Considering the emerging data about the role of adipokines in the pathogenesis of OA, the administration of drugs that influence their level is also intriguing. Metformin and alendronate were administered in mice with collagenase-induced OA (CIOA) as a monotherapy and in combination. Safranin O staining was used for the assessment of changes in subchondral bone and articular cartilage. Before and after treatment, serum levels of visfatin and biomarkers of cartilage turnover (CTX-II, MMP-13, and COMP) were assessed. In the current study, the combined administration of alendronate and metformin in mice with CIOA led to the protection against cartilage and subchondral bone damage. In mice with CIOA, metformin led to a decrease in visfatin level. In addition, treatment with metformin, alendronate, or their combination lowered the level of cartilage biomarkers (CTX-II and COMP), while the level of MMP-13 was not influenced. In conclusion, personalized combination treatment in OA according to clinical phenotype, especially in the early stages of the disease, might lead to the identification of a successful disease-modifying therapeutic protocol in OA.

The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease.

Intrahepatic oxidative stress is a key driver of inflammation and fibrogenesis in non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the role of extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) and extracellular nicotinic acid phosphoribosyltransferase (eNAPRT) for the detection of advanced fibrosis. eNAMPT and eNAPRT were tested in 180 consecutive biopsy-proven NAFLD patients and compared with liver stiffness (LS) and the FIB-4 score. eNAMPT was similarly distributed across fibrosis stages, whereas eNAPRT was increased in patients with advanced fibrosis (p = 0.036) and was associated with advanced fibrosis (OR 1.08, p = 0.016). A multiple stepwise logistic regression model containing significant variables for advanced fibrosis (eNAPRT, type 2 diabetes, age, male sex, ALT) had an area under the curve (AUC) of 0.82 (Se 89.6%, Sp 67.3%, PPV 46.7%, NPV 93.8%) when compared to that of LS (0.79; Se 63.5%, Sp 86.2%, PPV 66.0%, NPV 84.8%) and to that of the FIB-4 score (0.73; Se 80.0%, Sp 56.8%, PPV 44.9%, NPV 86.6%). The use of eNAPRT in clinical practice might allow for the better characterization of NAFLD patients at higher risk of disease progression.