Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Loeffelholz, Christian von; Möhlig, Matthias; Arafat, Ayman M.; Isken, Frank; Spranger, Joachim; Mai, Knut; Randeva, Harpal S.; Pfeiffer, Andreas F. H.; Weickert, Martin O.

doi:10.1530/eje-09-0737

Cited by 63 publications

(58 citation statements)

References 16 publications

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“…7,9,19 According to our data, vaspin increased with puberty in girls, but not in boys. Interestingly, vaspin was also found to be increased in patients with polycystic ovary syndrome 10 and treatment with estrogen/progesterone 20 or oral contraceptives 17 increased vaspin in polycystic ovary syndrome patients and healthy obese women. In the adipose tissue explants of polycystic ovary syndrome patients, estrogen was capable of stimulating vaspin protein expression, 10 which further supports the association of estrogen with vaspin levels.…”

Section: Discussionmentioning

confidence: 96%

“…Besides expression in WAT, we identified vaspin mRNA expression in the liver and potentially in the skin and the pancreas. Most studies found higher vaspin levels in adult women compared with men, 6,8,[16][17][18] whereas others did not. 7,9,19 According to our data, vaspin increased with puberty in girls, but not in boys.…”

Section: Discussionmentioning

confidence: 99%

“…This is consistent with findings in most, 5,9,10,23 though not all, adult studies. 17,18 One explanation might be that some studies included subjects with an extreme phenotype in terms of insulin resistance and thus the metabolic effects could have overcome any potential impact of sex steroids on serum vaspin. Considering that children present a phase early in the pathological career of obesity-related comorbidities, but on the other hand are free of possibly interfering drugs, such as oral antidiabetic medications, 10,16 our data may support the conclusion of an adaptive response of vaspin to impaired glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…This finding is coherent with the observation of a meal-related decline in vaspin levels 11,16 and may indicate that glucose and/or insulin may have acute suppressive effects of circulating vaspin levels and/or that food-related effects such as vagal activation are involved. Tan et al 10 identified glucose as a vaspin-releasing agent, at least in human omental adipose tissue explants, whereas Loeffelholz et al 17 observed a (non-significant) decrease of serum vaspin under conditions of euglycemic hyperinsulinemia. In summary, these results, together with the findings of Jeong et al, 11 underscore our suggestion of an acute suppressive effect of insulin on serum vaspin.…”

Section: Discussionmentioning

confidence: 99%

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

Körner¹,

Neef²,

Friebe³

et al. 2010

Int J Obes

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Background: Visceral adipose tissue-derived serine protease inhibitor (vaspin) has been suggested as a novel adipocytokine related to obesity and insulin sensitivity in adults. Design: 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. Results: 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. Conclusion: 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.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Körner¹,

Neef²,

Friebe³

et al. 2010

Int J Obes

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show abstract

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Abbreviations

DZHowever, in humans the association between serum vaspin levels and obesity variables is conflicting [3,4], and the relationship between circulating vaspin levels and glucose metabolism remains controversial [5,6]. In addition to these issues, it is still unknown whether serum vaspin levels are influenced by genetic or environmental factors.

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confidence: 99%

Impact of circulating vaspin levels on metabolic variables in elderly twins

et al. 2011

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Abbreviations DZHowever, in humans the association between serum vaspin levels and obesity variables is conflicting [3,4], and the relationship between circulating vaspin levels and glucose metabolism remains controversial [5,6]. In addition to these issues, it is still unknown whether serum vaspin levels are influenced by genetic or environmental factors. We therefore investigated the association of human serum vaspin levels with various anthropometric and clinical factors and elucidated the relative impact of genetic and environmental factors.Participants were identified through the Danish Twin Register as previously described [7]. A total of 298 elderly twins (126 monozygotic [MZ]: 49 pairs and 28 single twins aged 63-83 years; 172 dizygotic [DZ]: 56 pairs and 60 single twins aged 62-83 years) were enrolled in the study. All participants provided their written informed consent.

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Genetic dissection of serum vaspin highlights its causal role in lipid metabolism

Breitfeld,

Horn,

Le Duc

et al. 2023

Obesity

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ObjectiveVaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity‐related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated.MethodsA meta‐analysis of genome‐wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype‐Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured.ResultsA total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p < 5×10−8, explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low‐density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice.ConclusionsThe data show that serum vaspin is strongly determined by genetic variants within vaspin, which further highlight vaspin's causal role in lipid metabolism.

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Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Cited by 63 publications

References 16 publications

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

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

Impact of circulating vaspin levels on metabolic variables in elderly twins

Genetic dissection of serum vaspin highlights its causal role in lipid metabolism

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