Genetic dissection of serum vaspin highlights its causal role in lipid metabolism.
Obesity (Silver Spring)
; 31(11): 2862-2874, 2023 11.
Article
en En
| MEDLINE
| ID: mdl-37752728
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Serpinas
/
Metabolismo de los Lípidos
Tipo de estudio:
Clinical_trials
/
Systematic_reviews
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Obesity (Silver Spring)
Asunto de la revista:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania