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Despite continuous efforts to address classical risk factors for atherosclerosis, the battle to control the disease is far from over and atherosclerosis is still a major factor in all-cause mortality. To investigate the relations between early diagnosis and severity of coronary atherosclerosis we examined vaspin and nesfatin-1 levels, and the presence of fragmented QRS (fQRS) in admission electrocardiograms. We divided 168 patients into asymptomatic control (18%), <50% coronary artery stenosis (28%), >50% stenosis (31%) and myocardial infarction (MI) (23%) groups. Patients were also evaluated in anatomically significant (>50%stenosis ​+ ​MI) and non-significant atherosclerosis (control+<50%stenosis) groups. Vaspin and nesfatin-1 levels were measured using ELISA methods. Vaspin in MI and >50% stenosis groups was lower than in other groups (p ​< ​0.001). Nesfatin-1 in MI and >50% stenosis groups was lower only than in <50%stenosis group (p0.007). The presence of fQRS was higher in MI and >50% stenosis groups than other groups (p ​< ​0.001). In the anatomically significant atherosclerosis group, vaspin, nesfatin-1 and left ventricular ejection fraction (LVEF) values were lower while Gensini score and the presence of fQRS were higher (for all p ​< ​0.001). Lower vaspin levels and fQRS were related to in-hospital mortality (p ​< ​0.001 and p ​= ​0.02,respectively). Logistic regression analysis showed that male gender, diabetes mellitus, smoking, family history, lower LVEF, lower vaspin and fQRS were defined as independent risk factors for anatomically significant atherosclerosis (p ​= ​0.001). Our results indicate that low vaspin and fQRS were found to be novel independent risk factors for anatomically significant atherosclerosis and were predictors of mortality. [ABSTRACT FROM AUTHOR]

Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. Mice with HSC-selective deletion of NRP (ColCre/ Nrp1 loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1 l oxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. ColCre/ Nrp1 loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/ Nrp1 loxP mice compared to supernatant from Nrp1 loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage. • HSCs regulate hepatocyte steatosis that precedes liver fibrosis in alcohol-related liver disease. • HSC-derived Igfbp3 and SerpinA12 mediate lipid droplet formation in hepatocytes. • These results are recapitulated in samples from patients with alcoholic hepatitis. [ABSTRACT FROM AUTHOR]

• A novel nonessentials-guided in situ aptamer truncation was successfully developed. • This novel strategy was applied to a pair of aptamers, elucidating the binding sites. • A pair of novel truncated aptamers showed improved binding affinity and specificity. • This truncated pair was first realized in a sandwich-type electrochemical aptasensor. • This new aptasensor showed highly sensitive detection of vaspin in buffer and serum. Visceral adipose tissue-derived serpin (vaspin) is a biomarker associated with obesity and type 2 diabetes, both of which are prevalent and increasing in numbers worldwide. However, the sensitivity of existing aptasensors for vaspin detection does not yet match the reported serum levels. Aptamer sequences could contain nonessential nucleotides, which can be truncated out to potentially enhance their functionality and applicability. In this study, we developed a novel truncation method, a nonessentials-guided in situ truncation strategy to generate high-affinity aptamers by directly removing the nonessential portions of the aptamer sequences using exonucleases from the aptamer-protein complex kept stably. We applied this novel strategy to the original vaspin-binding aptamers, V1 and V49, resulting in two truncated aptamers, V1(3′-5′)–26 and V49(3′-5′)–30. These truncated aptamers showed enhanced binding affinity and specificity compared to their original aptamers. Confirmed to have different binding sites, this pair of truncated aptamers was successfully incorporated into a sandwich-type electrochemical aptasensor. This aptasensor achieved 16-fold higher sensitivity than the one using untruncated aptamers and enabled specific detection of vaspin in a buffer and even sensitive detection in serum within the physiological range. The reduced size of the aptamers could potentially cover the surface of the sensing platform, blocking nonspecific binding, thereby lowering the blank value, and improving the signal-to-noise ratio and limit of detection. This approach highlights the potential of the nonessentials-guided in situ truncation strategy for developing improved truncated aptamers, examining aptamer binding sites, and enhancing the analytical performance of biosensing platforms. [ABSTRACT FROM AUTHOR]

Highlights • Plasma vaspin levels increase significantly by inducing insulin resistance. • High-fat diet causes insulin resistance, but diazinon only causes disturbances in blood glucose level. • FoxO1 and PTEN genes have an important role in insulin resistance process. • Diazinon significantly increases the levels of vaspin in the plasma. Abstract Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated. Metabolic parameters implicated to the glucose and insulin statues such as homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were determined. DZN significantly inhibited almost 50% of the plasma cholinesterase (ChE) activity. A remarkable increase of MDA level was observed in groups that received DZN and DZN + HFD. Animals treated with DZN or DZN + HFD showed significant changes in reactive oxygen species (ROS) level. The level of plasma tumor Necrosis Factor alpha (TNF-α) was noticeably elevated in the exposed groups. The highest elevation in vaspin level was observed in HFD group followed by DZN treated animals. In all treated groups, insulin level significantly increased and also, the area under the curve (AUC0-180) values of plasma glucose heightened considerably. The histopathological micrographs of HFD + DZN treated group indicated a severe fatty change. The plasma concentration of DZN was significantly higher in the DZN-treated group in comparison to the DZN + HFD group. FoxO1 and PTEN mRNA levels were significantly overexpressed in the DZN and HFD exposed groups. In HFD treated group, PTEN expression significantly increased compared with the DZN and DZN + HFD groups. Consequently, in contrast to oxidative stress and inflammatory biomarkers, vaspin level would be a more reliable diagnostic factor when it comes to the insulin resistance. [ABSTRACT FROM AUTHOR]

This study showed that there is a positive correlation between serum Visceral Adipose tissue derived Serine Protease Inhibitor (VASPIN) level and polycystic ovary syndrome (PCOS). In previous studies, this relation was attributed to the generalization of higher amount of adipose tissue in patients with PCOS. However, we detected that VASPIN is significantly high in patients with PCOS regardless of BMI. Besides, the metabolic parameters such as fasting insulin, HOMA-IR, triglycerides and LDL-C levels were also increased in lean women with PCOS. [ABSTRACT FROM AUTHOR]

The purpose of our study was to investigate the effect of vaspin on myocardial ischemia reperfusion injury (MIRI) and explore the underlying mechanism. The MIRI model was induced with 30 min of left anterior descending (LAD) occlusion followed by 24 h of reperfusion. In vivo, the rats were randomly divided into five groups: (1) Sham, (2) MIRI, (3) MIRI + vaspin (10 mg/kg), (4) MIRI + vaspin (20 mg/kg) and (5) MIRI + vaspin (40 mg/kg). In vitro , H9C2 cells were assigned to five groups: (1) control, (2) hypoxia-re-oxygenation (H/R), (3) H/R + vaspin (1 μg/ml), (4) H/R + vaspin (2 μg/ml) and (5) H/R + vaspin (4 μg/ml). As a result, vaspin ameliorated MIRI and H/R in a dose-dependent manner, as evidenced by triphenyl tetrazolium chloride (TTC) staining, TUNEL Assay and MTT assay, respectively, meanwhile vaspin decreased the levels of creatine phosphokinase-isoenzyme (CK-MB) and lactate dehydrogenase (LDH) in rat serum, moreover, vaspin could reduce the contents of interleukin-1β (IL-1β), IL-18 and tumor necrosis factor alpha (TNF-α) in serum of rats and supernatant of H9C2 cells. Furthermore, vaspin down-regulated the expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor κB (NF-κB) in MIRI rats and H/R-induced H9C2 cells. In addition, patients with acute myocardial infarction (AMI) had lower levels of vaspin than patients without. In conclusion, vaspin might be a useful predictive biomarker in patients with AMI; furthermore, vaspin exhibits cardioprotective effects on MIRI which might act through inhibiting TLR4/NF-κB signaling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Aims Vaspin and irisin are novel cytokines proposed as potential new biomarkers of insulin resistance and endothelial dysfunction. This work is to investigate circulating levels of vaspin and irisin in patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease (CVD) to study potential association with disease risk. Materials and Methods Circulating levels of vaspin and irisin were assayed in serum from 135 T2DM patients (with and without CVD) and 70 control subjects by ELISA. Results Vaspin levels were significantly higher in T2DM patients than in control subjects (6798 ± 3540 pg/ml vs. 3215 ± 3209 pg/ml, p = 0.001) and in CVD patients than in non-CVD patients (7417.3 ± 3507.6 pg/ml vs. 6017.3 ± 3606.4 pg/ml, p = 0.001), with significant positive correlations with BMI, FPG, serum insulin and HOMA-IR. Irisin levels were significantly lower in T2DM patients than in controls (71.15 ± 67.57 ng/ml vs.127 ± 71.57 ng/ml, p = 0.004), and in CVD patients than in non-CVD patients (55.77 ± 54.82 ng/ml vs. 115.5 ± 67 ng/ml, p = 0.003), with significant correlations with HbA1c, HOMA-IR and BMI in diabetic patients, and with HbA1c and TG in CVD patients. Elevated levels of vaspin was associated with 1.7 times increased CVD risk (p = 0.001, OR = 1.7, 95%CI = 1.21–2.39), while lower levels of irisin associated with 1.6 times increased CVD risk (p = 0.007, OR = 1.6, 95%CI = 1.45–2.28). ROC analysis indicated serum vaspin and irisin as independent CVD risk biomarkers with sensitivity, 94% and 73.7%, and specificity, 74% and 74.1%; respectively. Conclusion Our results indicate that circulating vaspin and irisin are potential new independent CVD risk biomarkers in T2DM. [ABSTRACT FROM AUTHOR]

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease. Vaspin may modulate the inflammatory process, insulin resistance, and NAFLD. Omentin-1 is independently associated with hepatocyte ballooning. There is evidence of improvement in the adipokines level and histological hepatic steatosis following energy intake restriction and weight loss. The aim of the study was to evaluate the effects of Ramadan fasting on various circulating adipokines in NAFLD patients. Methods This study was conducted on 83 NAFLD patients, 42 cases who declared that they would fast during the month of Ramadan fasted and 41 controls who decided not to fast during Ramadan. Anthropometric parameters including weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and body fat percentage were measured before and after Ramadan. Dietary intake and physical activity levels were assessed by 24-h recall questionnaire and International physical activity questionnaire-short form (IPAQ-S), respectively. Serum adipokines including vaspin and omentin-1 were measured using commercial ELISA kit. Results Patients who fasted displayed a lower mean hip circumference and body mass index and considerable changes in serum vaspin and omentin-1 (p-value <0.05). The stepwise multivariate linear regression model revealed that the changes in weight, WHR, and dietary intakes were significant predictors of changes in serum adipokines. Conclusion There is a potential for fasting in improving several anthropometric indices in NAFLD patients. Additionally, fasting during Ramadan resulted in decreased levels of adipokines including vaspin and omentin-1. Studies with longer follow-up periods are required. [ABSTRACT FROM AUTHOR]

Vaspin expression is increased in white adipose tissue (WAT) of diet-induced obese mice and rats and is supposed to compensate HFD-induced inflammatory processes and insulin resistance in adipose tissue by counteracting pro-inflammatory gene expression in obesity. Multiple studies have also demonstrated strong anti-inflammatory effects in vascular and skin cells. Here, we used vaspin treated 3T3-L1 murine adipocytes as well as 3T3-L1 cells with stable vaspin expression to investigate the effect of exogenous and endogenous vaspin on inflammatory processes and insulin signaling in adipocytes. Our stably transfected cells secreted significant amounts of vaspin which was in the physiological range of ∼0.5 ng/ml in cell supernatants. Adipocyte differentiation was not affected by vaspin as expression of adipogenic marker genes as well as lipid accumulation after full differentiation was similar to control cells. We found that IL-1β induced expression and secretion of pro-inflammatory cytokines, such as IL-6, MCP1 and TNFα was significantly blunted in vaspin expressing 3T3-L1 cells. Treatment of 3T3-L1 cells with exogenous vaspin resulted in reduced cytokine-induced activation of the intracellular and pro-inflammatory NFκB signaling cascades (IKKα/β, IκB and NFκB). Moreover, endogenous vaspin positively affected insulin signaling by increasing insulin-stimulated phosphorylation of the key mediator protein kinase B (AKT). Together, we demonstrate anti-inflammatory effects of vaspin in 3T3-L1 adipocytes as well as increased insulin signaling by endogenous expression or exogenous treatment. The results provide evidence for potent anti-inflammatory action of vaspin not only in vascular cells but also in adipose tissue. [ABSTRACT FROM AUTHOR]

Objective: To determine whether serum vaspin levels can predict the success of ovulation induction and clomiphene resistance in anovulatory women with PCOS.Study Design: We designed a prospective case control study. The study population (n=49) was composed of infertile women with PCOS who underwent ovulation induction with clomiphene citrate. Patients were divided into two groups based on their treatment response. Group I consisted of patients with failed ovulation induction, and group II consisted of patients with successful ovulation induction. The study group characteristics, including age, BMI, waist-to-hip ratio, parity, hormone profiles, fasting insulin and glucose levels, HOMA-IR, triglycerides, and cholesterol and serum vaspin levels, were compared between the study groups.Result(s): There were 29 patients in Group I with failed ovulation induction (59.2%), and Group II consisted of 20 patients with successful ovulation induction (40.8%). No differences in characteristics were found. However, serum vaspin levels were significantly lower in responders achieving ovulation (p=0.001; p<0.01). At a vaspin level of 3.74, the sensitivity, specificity, positive predictive and negative predictive values were 90%, 72.4%, 69.2% and 91.3%, respectively. The odds ratio was determined to be 14.87 (95% CI: 3.41-64.88) as the cut-off point. No significant correlation was found in serum vaspin measurements between pregnant and non-pregnant patients who had achieved successful ovulation induction (p=0.5).Conclusion(s): Serum vaspin level may be a useful marker for the prediction of ovulation induction success in treatment with clomiphene citrate, and increased vaspin levels (≥3.74ng/mL) are correlated with clomiphene resistance in patients with PCOS according to our study results. [ABSTRACT FROM AUTHOR]

Vaspin is a glycoprotein with three predicted glycosylation sites at asparagine residues located in proximity to the reactive center loop and close to domains that play important roles in conformational changes underlying serpin function. In this study, we have investigated the glycosylation of human vaspin and its effects on biochemical properties relevant to vaspin function. We show that vaspin is modified at all three sites and biochemical data demonstrate that glycosylation does not hinder inhibition of the target protease kallikrein 7. Although binding affinity to heparin is slightly decreased, the protease inhibition reaction is still significantly accelerated in the presence of heparin. Glycosylation did not affect thermal stability. Image 2 • Vaspin (SERPINA12) is a glycoprotein with three glycosylation sites. • Glycosylation is important for proper protein secretion. • Vaspin glycosylation does not significantly affect target protease inhibition, cofactor binding and thermal stability. • Vaspin exhibits high in vitro plasma stability. [ABSTRACT FROM AUTHOR]

A new lateral flow strip assay (LFSA) using a pair of aptamers has been designed and successfully developed using a pair of aptamers-functionalized with gold nanoparticles (AuNPs). This new LFSA biosensor system utilizes a cognate aptamer duo binding to vaspin, a target protein, at the two different binding sites, and exhibited a sensitive and highly selective response to vaspin. A sandwich-type format in LFSA was developed based on biotin-labeled primary V1 aptamer immobilized on streptavidin coated membrane as a capturing probe and secondary V49 aptamer conjugated with AuNPs as a signaling probe. Using this LFSA, vaspin could be visibly observed within the detectable concentrations of vaspin up to 5 nM in both buffer and serum conditions. The sensitivity of this LFSA developed in this study was ranged from 0.137 to 25 nM in buffer and from 0.105 to 25 nM in spiked human serum, respectively. The limit of detection (LOD) of this LFSA was found to be 0.137 nM and 0.105 nM in buffer and spiked human serum condition, respectively. Therefore, this study has shown successful development of a simple yet effective LFSA for vaspin detection, and this development is not only limited to this target, but also other targets with a pair of aptamers available, without any special and laborious instrumentations. This system will be particularly useful as a screening tool for rapid on-site detection of any targets with a pair of aptamers generated. [ABSTRACT FROM AUTHOR]

Objective Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. Methods We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels. Vaspin expression was analyzed in isolated white and brown adipocytes during adipogenesis and in response to adrenergic stimuli. DNA-methylation within the vaspin promoter was analyzed to investigate acute epigenetic changes after cold-exposure in BAT. Results Our results demonstrate a strong induction of vaspin mRNA and protein expression specifically in BAT of both cold-exposed and high-fat (HF) or high-sugar (HS) fed mice. While obesogenic diets also upregulated hepatic vaspin mRNA levels, cold exposure tended to increase vaspin gene expression of inguinal white adipose tissue (iWAT) depots. Concomitantly, vaspin plasma levels were decreased upon obesogenic or thermogenic triggers. Vaspin expression was increased during adipogenesis but unaffected by sympathetic activation in brown adipocytes. Analysis of vaspin promoter methylation in AT revealed lowest methylation levels in BAT, which were acutely reduced after cold exposure. Conclusions Our data demonstrate a novel BAT-specific regulation of vaspin gene expression upon physiological stimuli in vivo with acute epigenetic changes that may contribute to cold-induced expression in BAT. We conclude that these findings indicate functional relevance and potentially beneficial effects of vaspin in BAT function. [ABSTRACT FROM AUTHOR]

Introduction Omentin and vaspin are adipokines manifesting a potentially protective action against obesity-associated metabolic disturbances. Aim Evaluation of relationship between serum concentrations of omentin and vaspin on one hand and indices of insulin resistance and anthropometric parameters in obese individuals on the other. Material and methods The studies were conducted on 64 individuals. The investigated group (37 obese patients) included the subgroup with normal glucose tolerance (NGT) and with abnormal glucose tolerance (AGT). The control group (n = 27) included healthy individuals with normal body weight. In all participants anthropometric analyses and biochemical tests, including estimation of omentin and vaspin concentrations were performed, and insulin resistance by HOMA-IR was evaluated. Results Concentrations of examined adipokines manifested no significant differences between the examined groups. Median values of the index defining ratio between studied adipokine and degree of insulin resistance, i.e. omentin/HOMA-IR, proved to be different in the investigated and the control group while no such difference could be noted in cases of vaspin/HOMA-IR indices. In the studied population a negative relationship was detected between serum concentration of omentin and systolic blood pressure (p < 0.04). Values of omentin/HOMA-IR index manifested a correlation with values of most anthropometric parameters (p < 0.0001), blood pressure (p < 0.0001) concentrations of TG (p < 000.1) and HDL (p < 0.0001), ISI basal (p < 0.00001), ISI gly (p < 0.0001), Quicki (p < 0.00001) and fasting insulinaemia (p < 0.00001). In the case of vaspin/HOMA-IR index only its positive relationship with HDL concentration was noted (p < 0.05). Conclusion In context of date of correlation, multiple regression and values of area of under receiver operating characteristics curve omentin, as compared to vaspin, seems to provide a better predictor of insulin resistance in obese individuals. [ABSTRACT FROM AUTHOR]

Background: Our previous study showed that patients with acute myocardial infarction (AMI) had lower levels of vaspin than patients without AMI. The aim of this study was to investigate the clinical significance of vaspin in patients with AMI.Methods: A total of 80 patients with AMI were enrolled. Plasma vaspin levels, clinical parameters, lipid profile, C reactive protein (CRP) were measured. All the patients were followed-up for 24±2 months for the occurrence of major adverse major cardiac events (MACEs).Results: During the follow-up, 48 patients experienced a MACE. The plasma vaspin concentrations in the MACEs-positive group were lower than those in the MACEs-negative group (0.156 ± 0.015 vs 0.314 ± 0.229ng/mL, p<0.001). Receiver operating characteristic curves showed that circulating vaspin concentration significantly differentiated patients with MACEs (p<0.001). The optimal cutoff value for predicting MACE was 0.259ng/mL. Then the patients were divided into vaspin>0.259ng/mL group and vaspin<0.259ng/mL group according to the plasma vaspin levels. Forty-five patients (74%) in the vaspin<0.259ng/mL group and three (16%) patients in the vaspin>0.259ng/mL group experienced a MACE. Multivariate survival analyses showed that the vaspin level (hazard ratio, HR 0.423) independently predicted the occurrence of MACEs. Compared with the results of echocardiography at admission, the improvement of LVEF in the vaspin>0.259ng/mL group was significant (54.3±7.6% to 61.2±4.7%, p<0.001), but the change of LVEF in the low vaspin group was not significant (51.3±9.7% to 52.5±10.9%).Conclusions: Vaspin might be a useful predictive biomarker in patients with AMI, and patients with low vaspin levels might have a high risk of a MACE. In addition, vaspin might have protective effects on the improvement of LVEF after AMI. [ABSTRACT FROM AUTHOR]

Background and objectives There is evidence based studies which show that plasma level of visfatin and vaspin in patients with type 2 diabetes mellitus elevate in comparison with healthy people. But there is no consistency in plasma visfatin and vaspin concentration between studies done on obese people. For this reason, the aim of this study is to investigate the serum level concentrations of visfatin and vaspin in obese women compared to normal weight women. Materials and methods The participants of this study consist of 43 women aged 20–50, and 43 healthy women with normal weight as a control group. They were matched for age and physical activity. 24 h food recall was used to collect dietary information from subjects. Moreover, blood sampling was taken to measure the blood levels of sugar, lipid profile, vaspin and visfatin. Results The mean serum level of visfatin was not statistically different between obese and normal weight women. But, the obese women had statistically higher mean serum level of vaspin than normal women ( p = 0.04). We found no relations between serum levels of vaspin with serum concentration of visfatin. Also, serum levels of these two adipokines were not related to the serum concentrations of fasting glucose, total cholesterol, low-density lipoprotein cholesterol and triglyserides and high-density lipoprotein cholesterol. Also, there was a significant positive relationship between carbohydrate intake and serum visfatin level in women participating to this study ( p = 0.018, r = 0.257). Conclusion The results of this study demonstrated that the level of serum vaspin was significantly higher in obese women. But there were no differences in serum levels of visfatin in comparison to normal weight women. Meanwhile this study demonstrated a positive relationship between serum levels of visfatin with dietary intake of carbohydrate, but no relationship between serum level of visfatin and vaspin in women participating in this study. [ABSTRACT FROM AUTHOR]

Association of serum and salivary adiponectin, apelin, visfatin and vaspin were studied in type 2 diabetes (T2DM) among Asian Indians. Their concentrations in periodontitis were also studied. In this cross-sectional analysis, men and women aged ≥35 years, with no history of diabetes, were screened for ≥3 risk factors for T2DM (n = 615). Eligible persons underwent a 75 gm oral glucose tolerance test and were categorized as Group A (Normal and Impaired Glucose Tolerant, n = 65) and Group B (Incident T2DM, n = 25). Screening for periodontitis was done. Saliva samples were collected in the morning. Participants refrained from food intake for about 2 hours prior to collection. Serum and saliva were stored for analysis. Serum adiponectin was low (p = 0.006) in T2DM and correlated with its salivary levels (r = 0.46, p < 0.001). Serum apelin levels were similar, but salivary concentrations were higher (p = 0.014) in T2DM. Higher serum (p = 0.016) and salivary (p = 0.03) visfatin levels were seen in T2DM. Vaspin levels showed no significant difference in the two groups, either in blood or saliva. Serum adipokines did not differ in the presence of periodontitis. In saliva, higher vaspin (p = 0.034) and lower visfatin (p = 0.018) concentrations were observed. The selected adipokines were measurable in saliva, in lower concentrations. Salivary adiponectin and visfatin measurements may be useful in studies on T2DM. • Adiponectin, apelin, visfatin and vaspin were measurable in saliva. • Salivary adiponectin was low in type 2 diabetes and mirrored its serum levels. • Higher serum and salivary visfatin levels were associated with type 2 diabetes. • Salivary adiponectin and visfatin measurements may be potential markers of type 2 diabetes. [ABSTRACT FROM AUTHOR]

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Aims Visceral adipose tissue-derived serpin (vaspin) was identified as a new adipocytokine. Many studies reported vaspin concentrations in obese subjects and type 2 diabetes mellitus (T2DM) patients. However, large variation in levels of vaspin seen in different studies may be attributable to differences of sample size. The aim of this study is to establish an accurate confidence interval of vaspin levels in obese subjects and T2DM patients using a large-scale meta-analysis. Methods Publications of the association between vaspin and obesity and T2DM in the databases of Medline, PubMed and EMBase were collected. The keywords included “vaspin” and “visceral adipose tissue-derived serpin”. Review manager 5.0 was used to process the data. Results For the analysis of obesity, 6 studies with 1826 participants were included in our meta-analysis; the level of vaspin was 0.52 ng/ml [95% confidence interval (CI)](0.10–0.93, P = 0.02) higher in obese subjects than that in non-obese healthy controls. Eleven studies with 1570 patients were included for the analysis of T2DM; the level of vaspin was 0.36 ng/ml [95%CI] (0.23–0.49, P < 0.00001) higher compared with that in healthy controls. Conclusions Significantly higher levels of serum vaspin were observed in obese subjects and T2DM patients. [ABSTRACT FROM AUTHOR]

Visceral adipose tissue–derived serine protease inhibitor (Vaspin) was found to have anti-inflammatory, anti-apoptosis, and pro-autophagy activities. Our investigation is aimed to ascertain the effect of Vaspin on hypoxia-evoked endothelial-mesenchymal transition (EndMT) in human cardiac microvascular endothelial cells (HCMECs). In vitro assays including CCK8, TUNEL, western blots, RT-qPCR to assess the effect of Vaspin on hypoxia-induced cell injuries, endothelial-mesenchymal transition (EndMT) and the inflammatory state in HCMECs. Transmission electron microscopy (TEM) was used to monitor autophagosome formation in HCMECs. The autophagy related proteins coupled with the critical effectors of PI3K/AKT-mTOR signaling pathway were also detected by western blots. In vivo assays including HE and ELISA to assess the effects of Vaspin on myocardial fibrosis pathology and type I and type III collagen in rats. Vaspin pretreatment dramatically dose-dependently restored the proliferative impairment and the induced EndMT in HCMECs by hypoxia. The Vaspin-pretreated HCMECs also presented with attenuated expression of increased IL-1β, TNF-α and IL-6 by hypoxia a dose-dependent manner. Vaspin alleviated rat MF. The impact of Vaspin is also related to the increased autophagy and activated PI3K/AKT-mTOR signaling pathway. The protective and pro-autophagy activity of Vaspin was antagonized by the PI3K/AKT-mTOR inhibitor LY294002. Vaspin ameliorated the hypoxia-stimulated cell injuries and EndMT by activating autophagy via PI3K/AKT-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Highlights: [•] Adipokines may be involved in acute ischemic stroke (AIS) (within 24h). [•] Higher visfatin and lower vaspin and ghrelin serum levels are associated with AIS. [•] Visfatin and ghrelin may be independent predictors of AIS. [•] Carotid stenosis and AIS showed pronounced effects on vaspin, visfatin and ghrelin. [•] Admission visfatin levels in AIS patients correlated with cardiovascular death/stroke/MI during follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Prevention of obesity and therapeutic weight loss interventions have provided only limited long term success. Therefore there is an urgent need to develop novel pharmacological treatment strategies, which target mechanisms underlying positive energy balance, excessive fat accumulation and adverse fat distribution. Adipokines may have potential for future pharmacological treatment strategies of obesity and metabolic diseases, because they are involved in the regulation of appetite and satiety, energy expenditure, endothelial function, blood pressure, insulin sensitivity, adipogenesis, fat distribution and insulin secretion and others. There are important road blocks on the way from an adipokine candidate to the clinical use a therapeutic compound. Such road blocks include an incomplete understanding of the mechanism of action, resistance to a specific adipokine, side effects of the adipokine and others. This review focuses on the potential of selected adipokines as therapeutic tools or targets and discusses important road blocks, which currently prevent their clinical use. [Copyright &y& Elsevier]

Abstract: Vaspin, an adipocytokine that has been isolated from the visceral adipose tissue, is a member of the serine protease inhibitor family. In humans, serum vaspin levels are correlated with body mass index (BMI) and obese women with polycystic ovary syndrome (PCOS). The present study is the first investigation to examine the association between vaspin rs2236242 gene polymorphism and risk of PCOS in Iranian patients. This case–control study was performed on 150 patients with PCOS and 150 healthy women. The vaspin genotypes were determined using tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Our finding showed that there are significant differences in genotype frequencies between case and control group regarding vaspin rs2236242 polymorphism (OR=0.59, CI=0.37–0.95, p=0.03). The A allele decreased the risk of PCOS (OR=0.67, CI=0.46–0.96, p=0.03) as compared to the T allele. There was no significant association between vaspin rs2236242 gene polymorphism and PCOS after adjusting genotypes for BMI. In conclusion, our data suggest a significant association between vaspin rs2236242 polymorphism and the PCOS but this relationship is affected by obesity status. [Copyright &y& Elsevier]

Abstract: Aims: In this study, we investigated the effects of visceral adipose tissue-derived serpin (vaspin), a newly discovered adipocytokine, on nuclear factor-kappa B (NF-κB) and its downstream molecules in proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-1 (IL-1), stimulated human endothelial EA.hy926 cells to elucidate the role of vaspin in the inflammatory states of endothelium. Methods: A NF-κB luciferase reporter system was constructed and stably transfected into human endothelial cell line EA.hy926. Following transfection, EA.hy926 cells were pretreated with various concentrations of vaspin (0–320ng/ml) before TNF-α and IL-1 stimulation. The transcription activity of NF-κB was determined using luciferase reporter assay. Expression levels of NF-κB downstream inflammatory cytokines, TNF-α, IL-1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Expressions of adhesion molecules and chemokines, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) were determined by quantitative real-time PCR (RT-PCR) and western blot in mRNA and protein levels, respectively. Results: Results showed that vaspin inhibited TNF-α and IL-1 mediated activation of NF-κB and its downstream molecules in a concentration-dependent manner (P <0.05). Conclusions: We conclude that vaspin protected endothelial cells from proinflammatory cytokines induced inflammation by inhibition of NF-κB and its downstream molecules. [Copyright &y& Elsevier]

Abstract: Objectives: Vaspin is a novel adipocytokine with potential insulin-sensitizing properties. Insulin resistance (IR) plays a role in the development and progression of atherosclerosis. However, the relationship between serum vaspin levels and atherosclerosis remains unknown. Therefore, we investigated whether vaspin was correlated with carotid intima-media thickness (c-IMT). Methods: Data for fasting vaspin levels of 201 subjects (78 men and 123 women aged over 40 years) were obtained from a general population in Japan. We obtained anthropometric parameters and blood chemistries, and calculated homeostasis model assessment-IR (HOMA-IR) index. C-IMT was measured by B-mode ultrasonography. The mean values of each parameter by tertiles of vaspin were compared with analysis of variance, and the associations of vaspin with IR and c-IMT were evaluated by multiple stepwise regression analysis. Results: Univariate analysis revealed that vaspin levels were positively correlated with BMI, insulin, HOMA-IR index, estimated glomerular filtration rate (eGFR), c-IMT and hypertensive medication. Multiple stepwise regression analysis revealed that HOMA-IR index, c-IMT and eGFR were significantly and independently associated with vaspin. We performed multivariate analyses with c-IMT as the dependent variable. Age, hypertensive medication and vaspin were significant for c-IMT. Moreover, a mediation analysis demonstrated that vaspin was significantly related to c-IMT, independently of IR. Conclusions: The present study not only confirmed the previous finding of the positive association of vaspin with IR but also demonstrated that serum vaspin level was positively associated with c-IMT, independently of IR in a general population. Our results may suggest a role of vaspin in atherosclerosis in humans. [Copyright &y& Elsevier]

Background: Cerebrovascular event is a clinical condition characterized by symptoms and findings pertaining to loss of focal cerebral function because of the vascular causes. Atherosclerosis has a forefront role in the pathogenesis of stroke. Inflammation has an important place in the formation of atherogenesis and atherosclerosis. Visceral adipose tissue–derived serpin (vaspin) is a new adipokine, which is identified recently, associated with obesity and diabetes and also has a proinflammatory characteristic. This study was intended to investigate the relation between vaspin and stroke and stroke and other risk factors. Methods: A total of 50 patients with stroke, as 28 men (56%) and 22 women (44%), and a total of 50 healthy individuals, as 25 men (50%) and 25 women (50%), were enrolled in the study. Blood samples were taken in the acute period (first 48 hours) in the patient group, and serum vaspin levels were measured. Vaspin level was also measured in the control group. The association of vaspin with the lipid parameters, gender, and the severity of internal carotid artery (ICA) stenosis in the patient group was evaluated. Stenotic plaques in ICA were classified as normal, mild (stenosis under 50%), moderate (stenosis 50%-69%), severe (stenosis 70%-99% to preocclusion), and occlusion. Results: No statistically significant difference was found between 2 groups in terms of age and gender (P > .05). Vaspin levels were found to be significantly higher in the patient group (164.73 ± 153.76 ng/mL) compared with the control group (116.21 ± 34.60 ng/mL) (P < .05). However, no relation was established between vaspin level and the severity of ICA stenosis. Conclusions: Vaspin levels have been shown to increase in acute ischemic stroke patients. The increased vaspin levels may vary depending on several factors in acute period of ischemic stroke. [Copyright &y& Elsevier]

Objective: Previous studies suggested that decreased serum vaspin levels were associated with coronary artery disease (CAD). The present study aimed to investigate the association between plasma vaspin levels and different states of CAD. Design and methods: A total of 162 patients with coronary angiography (CAG) proved that CAD was enrolled. Additional 103 patients complained with “chest discomfort” with negative CAG, and 60 normal subjects were enrolled in this study. The levels of plasma vaspin, adiponectin, clinical parameters, lipid profile and C reactive protein (CRP) were measured. Results: The levels of plasma vaspin were significantly lower in the CAD group (0.47±0.63μg/L) than those in the healthy group and CAG (−) group (all p<0.001). In CAD group, the pos hoc analysis showed that serum vaspin concentration in acute myocardial infarction group (0.21±0.19μg/L) was significantly lower than that in the unstable angina pectoris group (0.40±0.37μg/L) (p=0.012), and serum vaspin concentration in unstable angina pectoris was significantly lower than that in stable angina pectoris group (0.92±0.94μg/L) (p=0.013). The plasma vaspin concentration was also negatively correlated with the severity of CAD (1-vessel: 0.86±0.90μg/L; 2-vessel: 0.36±0.39μg/L; 3-vessel: 0.21±0.16μg/L). The plasma vaspin concentration in CAG (−) group with “chest discomfort” (1.93±2.57μg/L) was similar to the healthy control group (2.18±3.49μg/L). Conclusions: The plasma vaspin concentration correlated to the severity of CAD. Furthermore, plasma vaspin has a value of avoiding patients without CAD from unnecessary CAG. [ABSTRACT FROM AUTHOR]

Abstract: Background: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a recently identified adipokine. Studies suggest it is involved in many diseases such as obesity, diabetes and coronary artery disease (CAD). This study is to investigate the association of single nucleotide polymorphisms (SNPs) in vaspin with CAD and its potential mechanisms. Methods: A total of 1570 consecutive patients undergoing coronary angiography were enrolled and the genotypes were determined by TaqMan allelic discrimination. Serum vaspin concentrations and mRNA expression levels were determined by ELISA and RT-PCR, respectively. Reporter gene assay was performed to investigate the effect of polymorphism on vaspin promoter function. Results: After multivariate analysis, allele A of rs2236242 was found as an independent determinant of CAD (OR=1.32, p =0.004). Rs35262691 in vaspin promoter was associated with serum vaspin concentration and mRNA expression in peripheral blood mononuclear cells (PBMC) though no association had been found with CAD. Reporter gene assay further confirmed that CC genotype of rs35262691 had 2.1±0.4-fold higher activities than TT genotype in facilitating gene expression. Conclusions: Our results show that the variants of vaspin gene are associated with serum vaspin levels and risk for CAD in Chinese population. [Copyright &y& Elsevier]

Abstract: Metabolic syndrome (MeS) is associated with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. There is some evidence indicating that adipokines play a role in the development of MeS. The present study was aimed to investigate the impact of chemerin rs17173608 and vaspin rs2236242 gene polymorphisms with the risk of MeS in a sample of Iranian population. This case‐control study was done on 151 subjects with MeS and 149 without MeS, as defined by NCEP-ATPIII. Tetra amplification refractory mutation system‐polymerase chain reaction (T-ARMS-PCR) was designed to detect the polymorphisms. Our finding showed that there are significant differences in genotype frequencies between the groups regarding vaspin rs2236242 polymorphism (χ2 =18.74, p<0.0001). A significant protection against MeS was found for vaspin rs2236242 in allele and genotypes (Odd Ratio [OR]=0.52; 95% confidence interval [CI]=0.37–0.72; p=0.0001, T vs A; OR=0.49; 95%CI=0.29–0.82; p=0.007, TT vs TA and OR=0.17; 95%CI=0.07–0.40; p<0.0001, TT vs AA). Our finding showed positive association between chemerin rs17173608 polymorphism and risk of MeS (χ2 =7.70, p=0.021). The G allele increased the risk of MeS (OR=1.78; 95% CI=1.14-2.78; p=0.012) as compared to the T allele. In conclusion, our data suggest for the first time a significant association between vaspin rs2236242 and chemerin rs17173608 polymorphisms and the MeS in Zahedan, southeast Iran. Further studies with large sample size and different ethnicities are required to confirm our findings. [Copyright &y& Elsevier]

Abstract: Background: Adipose-tissue derivatives, known as adipokines, have been involved in the inflammatory-mediated metabolic and cardiovascular disorders of type 2 diabetes mellitus (T2DM). This study examined the association between novel adipokines and self-reported physical activity, a potential anti-inflammatory mediator. Methods: We enrolled 247 men and women with T2DM, free from overt cardiovascular disease. Based on a physical activity questionnaire, patients were classified into groups: A) sedentary, who did not report any physical activity or reported light activities<2h/week and B) active, referring to low or moderate-intensity physical activities>2h/week. Among them, 88 patients were randomly selected to perform a cardiorespiratory ergocycle testing. Clinical parameters, glycemic and lipid profiles, HOMA-IR, and serum levels of visfatin, apelin, vaspin, ghrelin and adiponectin were assessed. Results: With the exception of fat-mass, our groups did not differ in anthropometric parameters and pharmaceutical regimen. Active patients showed ameliorated glucose regulation, HOMA-IR, hsCRP and exercise capacity compared to sedentary counterparts (p<0.01). Active rather than sedentary patients showed lower visfatin (10.16±5.53ng/ml vs 14.77±8.48ng/ml, p=0.013), higher apelin (1.39±0.65ng/ml vs 1.04±0.35ng/ml, p=0.018) and adiponectin (11.82±3.06μg/ml vs 7.81±2.11μg/ml, p=0.033) levels. There were non-significant differences in the rest of parameters between groups. After adjusting for age, sex and BMI, physical activity along with hsCRP and ghrelin remained independent determinants of visfatin levels (R2 =0.328, p=0.032), while physical activity was independently associated with apelin (R2 =0.221, p=0.022). Conclusions: Self-controlled physical activity of, even, moderate intensity ameliorates adipokines, such as visfatin, apelin and adiponectin, in patients with T2DM. Prospective interventional studies will confirm our results. The ClinicalTrials.gov identifier is: NCT00306176. [Copyright &y& Elsevier]

Abstract: Aim: Vaspin and visfatin have emerged as novel adipokines, involved in atherosclerosis progression. The aim of the present study was to investigate the effects of atorvastatin and lifestyle modification on the above adipokines in hypercholesterolemic patients. Methods: One hundred four statin-free subjects with moderate cardiovascular risk (Framingham risk score of 10–20%) were randomly assigned to receive either atorvastatin 20mg per day (AT group, n =52) or lifestyle modification (LM, group, n =52). For comparison, age and gender-matched blood donors, without any chronic cardiovascular or metabolic disease served as healthy controls (HC group, n =40). Clinical and anthropometrical parameters, lipids, fasting glucose, serum vaspin, visfatin and insulin levels were obtained at the beginning and after 12weeks. Results: At the end of the study, intra-group and inter-group comparison revealed that atorvastatin administration considerably ameliorated most lipid parameters and downregulated hsCRP levels (p =0.002, p =0.041, respectively). Moreover, we observed a significant increase of vaspin concentrations after 12-week atorvastatin treatment (from 1.37±0.6ng/ml to 2.13±0.61ng/ml), as compared to baseline (p =0.007) and LM group (p =0.030). In standard multiple regression analysis, the atorvastatin-induced decrease of vaspin was independently associated with hsCRP reduction (p =0.015). On the other hand, within and between groups comparison revealed a non-significant (p >0.05) reduction of visfatin serum levels. In our study, lifestyle modification had totally modest influence on clinical and biochemical variables (p >0.05). Conclusion: In hypercholesterolemic patients with moderate estimated cardiovascular risk, atorvastatin administration reduced hsCRP and increased serum vaspin levels compared to lifestyle modification. The relation of those pleiotropic, non-lipid-lowering effects of statins with their clinical outcomes remains to be proved. [Copyright &y& Elsevier]

Abstract: Visceral adipose tissue-derived serpin (vaspin) improves glucose tolerance and insulin sensitivity in diet-induced obese mice. Chemerin may increase insulin sensitivity in adipose tissue and seems to be associated with several key aspects of metabolic syndrome. Decreased levels of omentin-1 are associated with increasing obesity and insulin resistance. Our study aimed to investigate the effects of vaspin, chemerin and omentin-1 acute administration on feeding and hypothalamic gene expression of peptides which play a key role in feeding regulation. 35 rats were injected into the arcuate nucleus (ARC) of the hypothalamus with either saline (n =8), vaspin (1μg/kg; n =9), chemerin (8μg/kg; n =9), or omentin-1 (8μg/kg; n =9). Food intake in the following 24h was recorded, thereafter rats were sacrificed. Total RNA was extracted from hypothalami and reverse transcribed to evaluate hypothalamic gene expression of agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin-A, cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC), by real-time reverse transcription polymerase chain reaction. Compared to vehicle, vaspin injection significantly decreased feeding, while chemerin and omentin-1 had no effect in the tested dose. Vaspin treatment significantly decreased NPY and increased POMC gene expression. Chemerin treatment led to a significant increase of both AgRP and POMC gene expression. Omentin-1 treatment did not modify gene expression of the investigated peptides. Therefore, vaspin is an adipokine triggering anorectic pathways in the hypothalamus, where reduction of NPY and increase of POMC mRNA levels mediate feeding inhibition. Chemerin and omentin-1 have no effect on feeding in the tested dose. [Copyright &y& Elsevier]

Abstract: Background: The association of novel adipokines, vaspin and visfatin, with atherosclerosis is still obscure. The present study aimed to investigate the relationship of those adipokines with the existence as well as the extent of coronary artery disease (CAD), suggesting a link between adiposity and atherosclerosis. Methods: We enrolled a total of 108 patients with angiographically proven stable, asymptomatic CAD and 65 healthy controls (HC) without cardiovascular diseases. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), vaspin and visfatin levels were assayed. Results: Serum levels of vaspin were significantly lower in subjects with CAD [0.91 (0.44–1.29) ng/ml] than healthy controls [1.42 (0.96–2.42) ng/ml] (p =0.009). Inversely, visfatin (p =0.016) and hsCRP (p <0.001) levels were considerably up-regulated in CAD vs HC group. Multivariate analysis demonstrated decreased vaspin and increased visfatin levels to correlate with CAD presence, independent of other cardiovascular risk factors (p <0.05). Standard multiple regression revealed HDL, LDL-C and vaspin to be independent determinants of Gensini score (R 2 =0.189, p =0.019). Notably, statin-free patients had even lower vaspin levels compared to statin users (p =0.018). Conclusions: Decreased vaspin and increased visfatin serum levels were observed in asymptomatic patients with CAD. Low vaspin concentrations seemed to correlate with CAD severity. [ABSTRACT FROM AUTHOR]

Background and Aims: The risks of insulin resistance and accelerated atherosclerosis are increased in chronic inflammatory diseases including rheumatoid arthritis (RA). Adipo-(cyto)kines are associated with insulin resistance, atherosclerosis and inflammation. This study aimed to determine serum adiponectin and vaspin levels and their associations with the predictors of atherosclerosis in RA and Behcet’s disease (BD). Methods: The study involved 56 patients with RA, 37 patients with BD, and 29 healthy controls (HC). Serum adiponectin and vaspin levels, homeostasis model assessment for insulin resistance (HOMA-IR) index, and common carotid intima-media thickness (IMT) were determined. Results: Serum adiponectin levels in both patient groups and serum vaspin level in only the RA group were higher, whereas serum vaspin level was lower in the active BD subgroup, compared to the HC group. However, adiponectin and vaspin levels were correlated with neither HOMA-IR index nor IMT in the RA group. Adiponectin level was correlated with DAS-28 and IL-6 level in the RA group, and it was higher in the active BD subgroup than in the inactive BD subgroup and the HC group. Conclusions: Adiponectin and vaspin levels are higher in RA but associated with neither HOMA-IR index nor IMT. Adiponectin is related with disease activity remarks in RA and BD. Therefore, it may be suggested that adiponectin may be involved in the regulation of inflammatory responses in inflammatory diseases. Moreover, in contrast to in RA, vaspin level declines in active BD, and these results suggest that different chronic inflammatory diseases exert different influences on either adipokines. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recently, visceral adipose tissue-derived serpin (vaspin) was identified as a potential insulin sensitizing adipokine, however, the factors determining the levels of circulating vaspin levels have not been fully understood. We investigated the association between adiposity, insulin resistance, lipid profiles and inflammatory markers including vaspin levels, and the effects of short-term intensive lifestyle modification on circulating vaspin levels in overweight or obese children. Methods: A total of 50 (25 boys, 25 girls) overweight or obese children aged 11 to 13years (average age: 12.0±0.9y, BMI: 25.35±86kg/m2) who complied with inclusion criteria participated in our study. To determine the association between adiposity, insulin resistance, lipid profiles and inflammatory markers including vaspin levels, cross-sectional analyses were performed. Thereafter, subjects underwent a tightly controlled seven-day intensive lifestyle modification including physical activity, dietary modification, and behavioral modification education in residence of a local university dormitory. Results: There was a negative correlation between vaspin concentration and fasting insulin (r =−.325, p <0.05) and homeostasis model assessment of insulin resistance (HOMA-IR) (r =−.331, p <0.05) when percent body fat was controlled. Multivariate linear regression analysis found serum vaspin level to be an independent predictor of insulin and HOMA-IR. Short-term intensive lifestyle modification significantly decreased vaspin levels by 39.28% (pre: .84±1.0, post: .51±1.0ng/ml, p <0.001) while adiponectin levels increased by 11.2% (pre: 6.50±2.89, post: 7.28±2.98ng/ml, p <0.01). In addition, short-term lifestyle modification significantly improved HOMA-IR (pre: 3.58±1.93, post 1.30±1.9, p <0.001) and lipid profiles. Conclusions: Serum vaspin level is one of the predictors for insulin resistance and was significantly reduced following short-term lifestyle modification. [Copyright &y& Elsevier]

Abstract: Aim: The aim of this study was to assess the vaspin and adiponectin concentrations on markers of insulin sensitivity and obesity in pubertal obese children and adolescents. Material and methods: Plasma vaspin and adiponectin level and its relationships with body mass index standard deviation score (BMI-SDS), insulin sensitivity and lipids were analyzed in 33 pubertal obese children (19 girls and 14 boys) and 36 healthy control children (18 girls and 18 boys) aged 11–16 years. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) and fasting glucose-to-insulin ratio (FGIR). Plasma vaspin and adiponectin concentrations were determined with radioimmunoassay. Results: Mean vaspin levels were found significantly higher and inversely, adiponectin levels were found significantly lower in obese pubertal group than control subjects. Vaspin levels were positively correlated with BMI-SDS, triglycerides, fasting insulin and HOMA-IR and negatively correlated with adiponectin levels and FGIR. Adiponectin levels were positively correlated with high density lipoprotein-chloesterol, FGIR and negatively correlated with vaspin, BMI-SDS, fasting insulin and HOMA-IR. Conclusion: We found higher vaspin and lower adiponectin levels in obese children and these adipokines were significantly correlated with insulin sensitivity indices in this age. [Copyright &y& Elsevier]

Abstract: Obesity is associated with accelerated atherosclerosis. Adipokines may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and modulating inflammation. Recently, visceral adipose tissue-derived serpin (vaspin) was identified as a novel adipokine related to obesity and its metabolic consequences. However, the regulation of vaspin serum concentrations in human atherosclerosis is unknown. We therefore assessed vaspin serum concentrations in 107 consecutive patients with carotid stenosis undergoing carotid endarterectomy (CEA) in relation to severity of atherosclerosis, measures of obesity and circulating markers of obesity and atherosclerosis. Vaspin serum concentrations were significantly lower in patients with carotid stenosis who experienced an ischemic event within 3 months before surgery compared to asymptomatic patients. However, circulating vaspin was not associated with measures of atherosclerosis severity as maximum percentage stenosis. Vaspin serum concentrations were indistinguishable before and after CEA. We found a significant correlation between vaspin and leptin serum concentrations supporting previous results that vaspin closely reflects body fat mass. In conclusion, our data show that low vaspin serum concentrations correlate with recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between circulating vaspin and parameters of atherosclerosis severity. [Copyright &y& Elsevier]

This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo. In vitro , chondrocytes were treated with interleukin-1β (IL-1β, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo , the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain. In vitro , in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1β. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo , the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats. In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage. [ABSTRACT FROM AUTHOR]

Vaspin is a protein present in human serum that can cause type-2 diabetes, obesity, and other cardiovascular diseases. We report fluorescent upconverting nanoparticles (UCNPs)-based lateral flow biosensor for ultrasensitive detection of Vaspin. A pair (primary and secondary) of cognate aptamers was used that has duo binding with Vaspin. UCNPs with a diameter of around 100 nm were used as a tag to label a detection probe (secondary aptamer). A primary aptamer (capture probe) was immobilized on the test zone. Sandwich type hybridization reactions among the conjugate probe, target Vaspin, and primary aptamer were performed on the lateral flow biosensor. In the presence of target Vaspin, UCNPs were captured on the test zone of the biosensor and the fluorescent intensity of the captured UCNPs was measured through a colorimetric app under NIR. Fluorescence intensity indicates the quantity of Vaspin present in the sample. A range of Vaspin concentration across 0.1–55 ng ml−1 with a Limit of detection (LOD) 39 pg ml−1 was tested through this UCNPs based LFSA with high sensitivity, reproducibility and repeatability, whereas it's actual range in human blood is from 0.1 to 7 ng ml−1. Therefore, this research provides a well-suited lateral flow strip with an ultrasensitive and low-cost approach for the early diagnosis of type-2 diabetes and this could be applied to any targets with a duo of aptamers generated. Schematic illustration of the configuration and measurement of the UCNPs based lateral flow aptasensor for VASPIN detection. Image 1 • A fluorescence based aptasensor was developed for quantitative detection of Vaspin. • Upconversion nanoparticles were utilized as highly sensitive signal label. • A covalent conjugate of secondary aptamer was developed as signaling probe, and detected in the nM range. • The sensor design is lateral flow based and can be applied for other targets if duo aptamers are available. [ABSTRACT FROM AUTHOR]

Vaspin, initially identified in visceral adipose tissue, is an adipokine, and administration of recombinant vaspin leads to lowering of the endoplasmic reticulum stress which is elevated in obesity or enhancement of insulin sensitivity. CCAAT/enhancer binding protein (C/EBP), as a basic leucine zipper transcription factor, plays a critical role in adipocyte development and glucose and lipid metabolisms in liver. The present study aimed to investigate the effect of C/EBPα on vaspin gene expression. The expression of hepatic vaspin was markedly decreased in liver-specific C/EBPα knockout mice. A reporter assay indicated that two C/EBP-responsive elements (CEBPREs) are necessary for C/EBPα-dependent induction of vaspin promoter activities. Furthermore, electrophoretic mobility shift assay showed that C/EBPα in mouse liver is capable of directly binding the two CEBPREs. These results suggest that C/EBPα positively regulates hepatic vaspin expression through two functional CEBPREs. Thus, vaspin is a novel C/EBPα target gene in the liver. • Vaspin is an adipokine that improves insulin sensitivity and glucose tolerance. • Expression of hepatic vaspin is decreased in liver-specific C/EBPα knockout mice. • C/EBPα directly binds to the two C/EBP-responsive elements in the vaspin promoter. • Vaspin genes are novel C/EBPα target genes in the liver. [ABSTRACT FROM AUTHOR]

Aim Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. Method The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. Results No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Conclusion Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. [ABSTRACT FROM AUTHOR]