Circulating Adipokine VASPIN Is Associated with Serum Lipid Profiles in Humans

Abstract

VASPIN, visceral adipose tissue‐derived serpin, is an adipokine ameliorating insulin resistance in obesity. Here, we investigated the role of VASPIN and its genetic variants in lipid metabolism. We measured serum VASPIN concentrations by ELISA in 823 metabolically well‐characterized Caucasian subjects (Sorbs from Germany). Furthermore, we genotyped 30 representative single nucleotide polymorphisms (SNP) in two independent cohorts with metabolic phenotyping, the Sorbs (N = 823) and Leipzig (N = 919), and conducted genotype–phenotype association analyses. Circulating VASPIN strongly correlated with triacylglycerol levels (TAG; p = 1.079 × 10−11), and moderately with apolipoprotein A1 and low‐density lipoprotein cholesterol (p = 0.026). Genetic variants in VASPIN were nominally associated with cholesterol, high‐density and low‐density lipoprotein (HDL‐chol, LDL‐chol), lipoprotein A, and apolipoprotein B as well as with TAG and free fatty acids (all p < 0.05 adjusted for age, sex, and body mass index [BMI]). Mendelian randomization analysis using VASPIN SNP as an instrumental variable showed borderline influence of VASPIN on LDL‐chol levels (p = 0.05). Associations of VASPIN and its genetic variation with metabolic traits suggest a role of VASPIN in human lipid metabolism.

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

“…In a previous study, we observed positive correlation between serum vaspin and TGs, which was further supported by MR analyses suggesting a causal impact on LDL‐chol [28]. In support of the metabolically beneficial action of vaspin in obesity [1, 2, 10, 28], the GECA and gene ontology enrichment analyses point out genes involved in lipid metabolic processes (e.g., low‐density lipoprotein receptor). Ultimately, our in vivo studies validated the involvement of vaspin in lipid metabolism by presenting reduced TG and lower FFA levels in vaspin‐treated mice.…”

Genome-Wide Association Study of Body Weight Traits in Chinese Fine-Wool Sheep

“…The NPC1 (niemann-Pick Type C) gene on chromosome 23 that correlated with yearling weight participates in controlling the steady state of animal energy metabolism and plays an important regulatory role in body weight and fat metabolism [40][41][42]. The SERPINA12 (serpin family A member 12) gene on chromosome 18 that correlated with adult weight is closely associated with animal body composition and lipid distribution, and could serve as a marker for lipid metabolism [43,44].…”

Loss-of-Function Variants in SERPINA12 Underlie Autosomal Recessive Palmoplantar Keratoderma

“…Vaspin was originally isolated from the visceral adipose tissue of the Otsuka Long-Evans Tokushima fatty rat, an experimental model for type 2 diabetes mellitus (Hida et al, 2005). Consequently, its function has mostly been studied in the context of obesity and insulin resistance (Breitfeld et al, 2019;Youn et al, 2008). Inhibition thickness was defined as the distance between the granular layer and the basement membrane (dotted line) and was measured at 20 randomly selected locations for each biopsy using NIS-Elements BR 3.2 software (Nikon).…”