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Genetic dissection of serum vaspin highlights its causal role in lipid metabolism.
Obesity 31, 2862-2874 (2023)
Objective: Vaspin (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. Methods: A 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. Results: A 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. Conclusions: The 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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association; Endothelial-cells; Kallikrein 7; Obesity; Population; Serpin; Inhibitor; Apoptosis; Glucose; Ligand
ISSN (print) / ISBN
1930-7381
e-ISSN
1930-739X
Journal
Obesity
Quellenangaben
Volume: 31,
Issue: 11,
Pages: 2862-2874
Publisher
Wiley
Publishing Place
111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology II (EPI2)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants
We thank Manuela Quandt and Eva Bge for excellent technical work and Noura Kabbani for proofreading the English language of the manuscript. Open Access funding enabled and organized by Projekt DEAL.