PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Breitfeld, J.* ; Horn, K.* ; Le Duc, D.* ; Velluva, A.* ; Marzi, C. ; Grallert, H. ; Friedrich, N.* ; Pietzner, M.* ; Völker, U.* ; Völzke, H.* ; Ahlqvist, E.* ; Aly, D.M.* ; Tuomi, T.* ; Baber, R.* ; Kratzsch, J.* ; Thiery, J.* ; Isermann, B.* ; Loeffler, M.* ; Klöting, N. ; Blüher, M. ; Stumvoll, M. ; Heiker, J.T. ; Tönjes, A.* ; Scholz, M.* ; Kovacs, P.*

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

Obesity 31, 2862-2874 (2023)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Altmetric
6.900
1.552
1
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Endothelial-cells; Kallikrein 7; Obesity; Population; Serpin; Inhibitor; Apoptosis; Glucose; Ligand
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1930-7381
e-ISSN 1930-739X
Journal Obesity
Quellenangaben Volume: 31, Issue: 11, Pages: 2862-2874 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30202 - Environmental Health
30201 - Metabolic Health
Research field(s) Genetics and Epidemiology
Helmholtz Diabetes Center
PSP Element(s) G-504091-002
G-506500-001
G-506501-001
G-554800-001
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.
DOI 10.1002/oby.23882
WOS ID 001074556000001
Scopus ID 85172085596
PubMed ID 37752728
Erfassungsdatum 2023-10-18
[➜Report correction]