Serum Vaspin Concentrations Research Articles

Analysis of a rare functional truncating mutation rs61757459 in vaspin (SERPINA12) on circulating vaspin levels

A recent genome-wide association study suggests that genetic variation within the vaspin gene might contribute to the variability in circulating serum visceral adipose tissue-derived serine protease inhibitor (vaspin) concentrations. Here, we analyzed the functional consequences of the rare variant rs61757459 predicting a premature stop codon and its impact on circulating serum vaspin concentrations. In order to identify genetic variation, we sequenced the vaspin gene in 48 nonrelated Caucasian subjects. Rs61757459 was subsequently genotyped in three metabolically well-characterized German cohorts (N = 4,019). We addressed the impact of rs61757459 on the crystal structure of vaspin and investigated its effects on vaspin expression in vivo as well as in vitro using various cell lines (Escherichia coli, HEK293). Along with previously reported common genetic variants, sequencing of vaspin revealed a rare variant (rs61757459; minor allele frequency: 1 %) which predicts a premature stop codon p.R211X. Heterozygous carriers of this mutation had lower circulating vaspin levels when compared with noncarriers. In silico structure analysis of the truncated vaspin, which was estimated to be 24.5 kDa, suggested misfolding and potential instability due to the absence of core structural domains. Indeed, the truncated protein was detected after recombinant expression in E. coli and in lysate, but not in supernatant of HEK293 cells. We conclude that rs61757459 is a functional mutation that results in a truncated protein whose instability likely results in reduced serum vaspin levels. A rare variant (rs61757459) in vaspin coding for the stop codon p.R211X is related to lower circulating vaspin concentrations. Structure analysis suggests misfolding and instability due to the absence of core structural domains. The truncated protein is detectable after recombinant expression in E. coli and in lysate, but not in supernatant of HEK293 cells.

Role of Vaspin in Human Eating Behaviour

ObjectiveThe adipokine vaspin (visceral adipose tissue derived serine protease inhibitor, serpinA12) follows a meal-related diurnal variation in humans and intracerebroventricular vaspin administration leads to acutely reduced food intake in db/db mice. We therefore hypothesized that vaspin may play a role in human eating behaviour.Materials and MethodsWe measured serum vaspin concentrations in 548 subjects from a self-contained population of Sorbs (Germany) who underwent detailed metabolic testing including eating behaviour assessments using the three-factor eating questionnaire. In addition, genetic variation within vaspin was assessed by genotyping 28 single nucleotide polymorphisms (SNPs) in all study subjects.ResultsSerum vaspin concentrations correlated positively with restraint, disinhibition and hunger (all P<0.05), although the correlations did not withstand further adjustments for age, gender and BMI (all P>0.05). Independent of observed correlations, genetic variants in vaspin were associated with serum vaspin levels but showed no significant association with any of the eating behaviour phenotypes after accounting for multiple testing (P≥0.05 after adjusting for age, gender and BMI).ConclusionOur data suggest that serum vaspin concentrations might modulate human eating behaviour, which does not seem to be affected by common genetic variation in vaspin.

Insulin Administration Acutely Decreases Vaspin Serum Concentrations in Humans

It has been hypothesized that insulin might mediate meal-related diurnal variation in vaspin serum concentrations. We therefore investigated whether insulin affects serum vaspin levels in humans. Vaspin serum concentrations were determined by ELISA in 10 healthy individuals, who underwent an insulin tolerance test (ITT) for the evaluation of pituitary ACTH and growth hormone reserve. The ITTs were started 08:00 am after an overnight fast with a bolus i.v. insulin dose of 0.15 IU/kg body weight (Actrapid™). Blood samples were taken at -15, 0, 15, 30, 60, 90, and 120 min after insulin administration. 15 min after insulin administration, vaspin serum concentrations decreased by 19 ± 6%, continued to decrease by 42 ± 12% at 60 min and returned to 88 ± 7% of initial values 120 min after insulin administration. Our data suggest that meal-related changes in serum vaspin concentrations might be mediated by insulin.

Fibronectin Gene Expression in Human Adipose Tissue and Its Associations with Obesity-Related Genes and Metabolic Parameters

Limited data are available on the in vivo expression of fibronectin, one of the main extracellular matrix components. We investigated the expression of fibronectin in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the associations of leptin, adiponectin, and vaspin gene expression with metabolic parameters in obese women. We recruited female subjects undergoing bariatric surgery for obesity (n = 24) and patients undergoing benign gynecological surgery as the control group (n = 23). We measured anthropometric variables, abdominal fat distribution, metabolic parameters, serum concentrations of leptin, adiponectin, and vaspin, and depot-specific mRNA expression of fibronectin, leptin, adiponectin, and vaspin. Fibronectin expression in both VAT and SAT was significantly lower in the obese group than in the control group. Fibronectin expression in both VAT and SAT were negatively correlated with body mass index or waist circumference, with higher prominence in VAT. In multiple regression analysis, fibronectin expression in both VAT and SAT was negatively correlated with serum leptin concentration. Fibronectin expression in VAT was negatively correlated with leptin expression in VAT. Additionally, fibronectin expression in SAT was negatively correlated with leptin expression in SAT and positively correlated with adiponectin expression in VAT and SAT. We found significant negative associations between depot-specific fibronectin expression in human adipose tissue and obesity indices and obesity-related biomarkers. Our results suggest that fibronectin expression may contribute to obesity and metabolic dysregulation in humans.

Gender-dependent Effects of Metformin on Vaspin and Adiponectin in Type 2 Diabetes Patients: A Randomized Clinical Trial

The aim of the study was to assess the effects of metformin on serum concentrations of vaspin and adiponectin in diabetes. Randomized clinical trial of 99 newly diagnosed, medication-naïve, type 2 diabetes patients (NCT01521624) was carried out. Patients were randomly assigned to either metformin 1 000 mg daily plus advice for exercise and lifestyle modification (n=50) or modification alone (n=49). A third group of 50 normoglycemic subjects were also enrolled to compare adipokine concentrations between healthy and diabetes subjects. Serum concentrations of adipokines were measured at baseline and after 12 weeks using ELISA method. Healthy subjects had significantly higher adiponectin levels, but lower concentrations of serum vaspin (p<0.001 in all cases). Vaspin and adiponectin concentrations were 23% and 26% higher in women compared with men. Vaspin dropped significantly after 3-month metformin therapy only in women (1.36 vs. 0.98, p=0.003 in women and 1.31 vs. 1.20, p=0.335 in men). Metformin therapy did not change adiponectin concentration in neither women nor men of the case group (12.66 vs. 12.44 p=0.699 in women and 10.13 vs. 10.94 p=0.253 in men). Comparing case and control groups, metformin decreased vaspin levels more significantly than lifestyle modification in the final multivariate model after controlling for potential confounders only in women (p=0.002) but not men (p=0.896). Conversely, adiponectin levels increased more significantly in the control group, again only in women (p=0.012 and 0.579 for women and men, respectively). Our findings suggest that metformin therapy reduces vaspin concentration in a gender-specific manner. Metformin exerts little benefit in increasing adiponectin levels in diabetes patients.

Association of vaspin gene polymorphisms with coronary artery disease in Chinese population and function study

BackgroundVisceral 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. MethodsA 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. ResultsAfter 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. ConclusionsOur results show that the variants of vaspin gene are associated with serum vaspin levels and risk for CAD in Chinese population.

650 Umbilical Cord and Fifth Day Serum Vaspin Concentrations in Small, Appropriate and Large for Gestational Age Neonates

Background and AimVaspin is a visceral adipose tissue derived serin protease inhibitor which has an insulin sensitizing effect. It is correlated with insulin resistance and glucose metabolism and it improves...

Vaspin Serum Concentration in Patients with Type 2 Diabetes and Carotid Plaque

To examine whether there is an association between the serum concentration of vaspin and the presence of carotid plaque in early stage type 2 diabetes mellitus (T2DM). Patients (n = 61) with T2DM within 3 years of diagnosis were divided into those with and those without carotid plaque. Fasting serum vaspin levels, measured by enzymelinked immunosorbent assay, and blood pressure were compared between these two groups and also with an age-matched, apparently healthy control group (n = 26). Fasting serum vaspin concentrations were significantly higher in patients with T2DM without carotid plaque than in controls, but significantly lower in T2DM patients with carotid plaque than in those without. Multivariate logistic regression analysis showed a significant positive association between the presence of carotid plaque and systolic blood pressure and a significant inverse association between the presence of carotid plaque and fasting serum vaspin concentration. A significant inverse association was found, in patients with T2DM within 3 years of diagnosis, between serum vaspin concentration and the presence of carotid plaque.

Genetic variation in the vaspin gene affects circulating serum vaspin concentrations

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine potentially linking obesity, insulin resistance and type 2 diabetes. Here, we searched for genetic determinants that could explain the variability in serum vaspin concentrations. First, we conducted a genome-wide association study (GWAS) for serum vaspin in the Sorbs cohort (N=826). Subsequently, 26 single-nucleotide polymorphisms (SNPs) covering genetic variation in the vaspin locus were genotyped in the Sorbs. In addition, we measured serum vaspin concentrations in 1806 samples from Augsburg/the Cooperative Health Research in the Region of Augsburg (KORA) for replication of the association signals. Finally, we conducted association analyses of vaspin SNPs with metabolic traits in the Sorbs (N=1013), KORA (N=1813) and a further cohort from Germany (Leipzig: N=1857). Six SNPs mapping between serpinA1 and serpinA4, including the vaspin locus, on chromosome 14 reached P-values < or = 10(-8) in the GWAS in the Sorbs. The fine mapping of variants within the vaspin locus in the Sorbs and subsequent replication in the KORA sample revealed several SNPs significantly associated with serum vaspin concentrations reaching P-values of up to 10(-35). However, no significant association with type 2 diabetes or related traits was found in either cohort after the Bonferroni correction for multiple comparisons. Our data show that the variability in serum vaspin concentrations might be explained by its genetic variants.

Umbilical cord and fifth-day serum vaspin concentrations in small-, appropriate-, and large-for-gestational age neonates

Vaspin is a visceral adipose tissue-derived serine protease inhibitor that has an insulin-sensitizing effect. It is correlated with insulin resistance and glucose metabolism, and it improves glucose tolerance. The aim of this study was to determine and compare serum vaspin and insulin concentrations in small-for- gestational age (SGA), appropriate-for-gestational age (AGA), and large-for-gestational age (LGA) infants at birth and fifth postnatal day. Eighty-two neonates were divided into three groups: SGA (n=22), AGA (n=30), and LGA (n=30). Mothers' age, gestational week, mode of delivery, and maternal diseases, such as diabetes, pre-eclampsia, and eclampsia were recorded. Blood for vaspin, insulin, and glucose was collected from the cord at birth and from a peripheral vein on the fifth postnatal day. At birth, there were no statistically significant difference in serum insulin concentrations among the three groups, whereas cord serum vaspin concentrations were significantly higher in the SGA group (χ2=8.158, p<0.05). Serum glucose and vaspin levels on the fifth postnatal day had no significant difference among three groups (p<0.05). Circulating vaspin concentrations were not associated with the sex of the infant and delivery route. Cord vaspin levels are significantly higher in SGA neonates than in AGA or LGA neonates. The fetal programming hypothesis proposes that many adulthood diseases originate from the adaptation that the fetus makes when it is undernourished. High cord-vaspin levels in SGA infants may be one of the adaptations for increased risk for adult metabolic diseases.

Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 atSERPINA12Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population

Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats. We investigated genetic and nongenetic factors that define serum concentrations of vaspin. Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138). The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 ± 0.04 vs. 0.86 ± 0.02 ng/ml; P < 0.01). Both in T2D and genotyped Japanese population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 ± 0.4 ng/ml), CA (18.4 ± 9.6 ng/ml), and AA (30.5 ± 5.1 ng/ml) (P < 2 × 10(-16)). Putative GATA-2 and GATA-3 binding consensus site was found at rs77060950. Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950.

Vaspin in obesity and diabetes: pathophysiological and clinical significance

Vaspin (visceral adipose tissue-derived serpin; serpinA12) was originally identified as an adipokine, which is predominantly secreted from visceral adipose tissue in Otsuka Long-Evans Tokushima fatty (OLETF), an animal model of obesity and type 2 diabetes. Consistent with that higher vaspin serum concentrations and increased vaspin mRNA expression in human adipose tissue were found to be associated with obesity, insulin resistance, and type 2 diabetes in humans. However, the mechanisms how vaspin secretion may be linked to deterioration of glucose metabolism and insulin sensitivity are not entirely understood. Vaspin serum concentrations show a food intake-related diurnal variation. Vaspin is also expressed in the skin, hypothalamus, pancreatic islets, and stomach. Administration of vaspin to obese mice improves glucose tolerance, insulin sensitivity, and reduces food intake. Until now molecular target(s) of vaspin and its mode of action are unknown. Thus, identification of the proteases, which are inhibited by vaspin may lead to the development of novel strategies in the treatment of obesity, diabetes and insulin resistance. This review discusses the clinical relevance of vaspin in the pathophysiology of obesity and type 2 diabetes.

Short-term effect of weight loss through restrictive bariatric surgery on serum levels of vaspin in morbidly obese subjects

The aims of this study were to evaluate the short-term effects of laparoscopic restrictive bariatric surgery (LRBS) on plasma levels of vaspin and the potential associations of changes in vaspin levels with changes in anthropometric indices, insulin-resistance and dietary intake. Thirty, severely obese subjects (21 female; mean age, 32.5 years) with a mean body mass index (BMI) of 44.1 ± 4.9 kg/m(2) underwent LRBS. Measurements of anthropometric indices, dietary intakes, physical activity and plasma vaspin concentrations were performed prior to, and six weeks after LRBS. Insulin-sensitivity was estimated using the homeostasis model assessment of insulin-resistance (HOMA-IR). Six weeks after LRBS, BMI decreased to a mean of 38.4 ± 4.9 kg/m(2). Significant reductions were also observed in waist circumference (WC), daily intakes of calorie, fat and protein, and plasma concentrations of triglyceride. No significant change was observed in fasting levels of insulin, blood sugar or HOMA-IR. Vaspin decreased significantly (0.26 ± 0.17 vs 0.36 ± 0.20, p=0.048) following surgery. While the percentage change of vaspin was not correlated with percent changes in anthropometric indices and HOMA-IR, it correlated positively with the percentage change in intake of calories, fat and protein: this correlation remained significant even after adjustment for sex and changes in WC and HOMA-IR. Our study suggests that LRBS decreases the serum vaspin concentrations in parallel with the restriction of dietary intake. Furthermore, decreased levels of vaspin early after LRBS seem more likely to result from decreased dietary intake rather than weight-loss-induced insulin sensitivity improvement.

Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus

Aim To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction. Methods Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. Result Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71 ± 0.93 ng/ml versus 2.69 ± 2.02 ng/ml, p = 0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452 ± 0.254 ng/ml versus 0.409 ± 0.275 ng/ml, p > 0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR) = 1.71, 95% confidence interval (1.30–2.25); p < 0.0001]. Conclusion The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group.

Vaspin,obesity,and type 2 diabetes

Vaspin,a serine protease inhibitor derived from visceral adipose tissue,has been identified as an adipokine with insulin-sensitizing effects in a rat model of type 2 diabetes.Recent studies showed that the administration of recombinant human vaspin significantly improved insulin sensitivity and glucose tolerance,and reversed the expression of genes that may promote insulin resistance in diet-induced obese mice.However,the regulation of serum vaspin concentration in individuals with insulin resistance,and the association of vaspin with obesity,type 2 diabetes,and insulin resistance related disorders remain unclear. Key words: Adipokine; Vaspin; Obesity; Diabetes mellitus,type 2; Insulin resistance

Molecular mechanism of the insulin sensitizing adipokine vaspin

Introduction: Obesity represents a fast growing health problem that is reaching epidemic proportions worldwide and is associated with an increased risk of premature death. Obesity significantly increases the risk of developing type 2 diabetes mellitus, hypertension, coronary heart disease, stroke, and several types of cancer. Vaspin (visceral adipose tissue-derived serpin) was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes (T2D). We recently reported that elevated vaspin serum concentrations are associated with obesity and impaired insulin sensitivity in humans. It has therefore been postulated that increased vaspin expression and secretion could represent a compensatory mechanism associated with obesity, severe insulin resistance, and type 2 diabetes. Although, antiprotease properties have been suggested as mechanism of vaspin action, until now a protease substrate of vaspin has not been identified.

Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects

Vaspin (visceral adipose tissue-derived serpin) was first identified as an adipokine in a rat model of type 2 diabetes, in which it is predominantly secreted from visceral adipose tissue. Serum concentrations of vaspin show a food intake-related diurnal variation. We therefore tested the hypothesis that vaspin plays a role in the regulation of food intake. Vaspin levels in the hypothalamus and human stomach were determined by western blotting. The cerebrospinal fluid concentration of vaspin was measured in five healthy volunteers using an ELISA. Fed 11-week-old female db/db mice were given intraperitoneal injections of 1 mg/kg body weight of vaspin (n = 6) or saline (n = 6) on experimental days 1, 3 and 4. Changes in food intake and fed plasma glucose concentrations were determined after one intracerebroventricular administration of either 1 μg vaspin or artificial cerebrospinal fluid into 11-week-old female db/db (n = 8) and C57BL/6 mice (n = 8) up to 6 days after injection. We detected vaspin in the hypothalamus of db/db and C57BL/6 mice and in the cerebrospinal fluid of healthy individuals. Both peripheral and central vaspin administration decrease food intake in obese db/db and lean C57BL/6 mice. In db/db mice, vaspin treatment is associated with sustained glucose-lowering effects for at least 6 days after injection. In addition, we demonstrated expression of the gene encoding vaspin in the gastric mucosa in humans, and found that this was subject to regional variations. Our data suggest a previously unrecognised role of vaspin in the regulation of food intake. We postulate that vaspin inhibits a protease that degrades an anti-orexigenic factor.

Relationship between vaspin gene expression and abdominal fat distribution of Korean women

Visceral adipose tissue-derived serpin (vaspin) is a novel adipokine that is thought to have insulin-sensitizing effects. We investigated vaspin mRNA expression in abdominal adipose tissue and examined how gene expression related to abdominal fat distribution and metabolic parameters in Korean women. We measured anthropometric variables, metabolic parameters, serum vaspin concentration, and vaspin mRNA expression in abdominal adipose tissue obtained from women who underwent abdominal gynecological surgery and were aged 18-67 years (n = 85). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area were measured in 40 subjects using computed tomography (CT). Vaspin expression was analyzed by real-time quantitative RT-PCR according to abdominal fat distribution. Vaspin mRNA expression was greater in adipocytes than in stroma/vascular cells. In the total subjects, vaspin expression was significantly higher in SAT than in VAT. Vaspin expression in SAT in subcutaneous fat type (VSR ≤ 0.3) was significantly higher than in visceral fat type (VSR > 0.3), although vaspin expression in VAT was similar between subcutaneous and visceral fat type. There was a significant negative correlation between vaspin expression in SAT and VAT area (r = -0.55, p = 0.001). Serum vaspin concentration was significantly correlated with fasting insulin (r = 0.30, p = 0.02), HOMA-IR (r = 0.29, p = 0.02), and the ratio of vaspin expression in VAT to vaspin expression in SAT (r = 0.41, p = 0.04). Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in SAT decreased as VAT area increased.

Effects of Weight Reduction on Serum Vaspin Concentrations in Obese Subjects: Modification by Insulin Resistance

Visceral adipose tissue-derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12-week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMA(IR)). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMA(IR) group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMA(IR) group was positively correlated with change in BMI and negatively correlated with initial HOMA(IR) level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMA(IR) group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.

Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children

Visceral adipose tissue-derived serine protease inhibitor (vaspin) has been suggested as a novel adipocytokine related to obesity and insulin sensitivity in adults. We quantified vaspin serum concentrations in 65 lean and 67 obese children and aimed to evaluate the relationship of vaspin with physical development, obesity, and metabolic and cardiovascular phenotypes in children. We further assessed the acute vaspin response to glucose provocation in 20 obese adolescents and evaluated tissue expression patterns of vaspin in humans. Vaspin levels were significantly higher in girls than in boys. In girls, vaspin increased with age and pubertal stage, whereas there was no change with development in boys. Obese girls had lower vaspin serum levels than those of lean controls, but there was no significant correlation with body mass index (BMI). Independent of sex, age and BMI, lower vaspin was associated with better insulin sensitivity, with higher systolic blood pressure and impaired endothelial function. In response to glucose provocation during an oral glucose tolerance test, vaspin serum levels declined by approximately 25% in adolescents with hyperinsulinemia, whereas there was no significant decline in normoinsulinemic patients. In support of our clinical data, we not only confirmed vaspin mRNA expression in adipose tissue but also found consistent expression of vaspin in the liver and indications for expression in the pancreas and the skin. We showed that gender differences in circulating vaspin levels develop during pubertal progression in girls. Although vaspin's association with obesity remains controversial, vaspin was increased with worsening insulin resistance already in children and was acutely down-regulated following glucose provocation in insulin-resistant adolescents independent of obesity. Besides adipose tissue, vaspin expression in the liver and the pancreas may potentially contribute to circulating vaspin levels and their regulation.