Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity.
Humans
Adipose Tissue
/ metabolism
Diabetes Mellitus, Type 2
/ genetics
Interferon Regulatory Factors
/ metabolism
Myeloid Differentiation Factor 88
/ metabolism
NF-kappa B
/ metabolism
Obesity
/ genetics
Toll-Like Receptor 3
/ metabolism
Toll-Like Receptor 9
/ metabolism
Toll-Like Receptors
/ genetics
IRFs
TLRs
adipose tissue
inflammation
obesity
steroid receptor RNA activator 1/SRA1
type-2 diabetes
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
11 12 2022
11 12 2022
Historique:
received:
05
11
2022
revised:
04
12
2022
accepted:
09
12
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
27
12
2022
Statut:
epublish
Résumé
Steroid receptor RNA activator gene (SRA1) emerges as a player in pathophysiological responses of adipose tissue (AT) in metabolic disorders such as obesity and type 2 diabetes (T2D). We previously showed association of the AT SRA1 expression with inflammatory cytokines/chemokines involved in metabolic derangement. However, the relationship between altered adipose expression of SRA1 and the innate immune Toll-like receptors (TLRs) as players in nutrient sensing and metabolic inflammation as well as their downstream signaling partners, including interferon regulatory factors (IRFs), remains elusive. Herein, we investigated the association of AT SRA1 expression with TLRs, IRFs, and other TLR-downstream signaling mediators in a cohort of 108 individuals, classified based on their body mass index (BMI) as persons with normal-weight (N = 12), overweight (N = 32), and obesity (N = 64), including 55 with and 53 without T2D. The gene expression of SRA1, TLRs-2,3,4,7,8,9,10 and their downstream signaling mediators including IRFs-3,4,5, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), and nuclear factor-κB (NF-κB) were determined using qRT-PCR and SRA1 protein expression was determined by immunohistochemistry. AT SRA1 transcripts' expression was significantly correlated with TLRs-3,4,7, MyD88, NF-κB, and IRF5 expression in individuals with T2D, while it associated with TLR9 and TRAF6 expression in all individuals, with/without T2D. SRA1 expression associated with TLR2, IRAK1, and IRF3 expression only in individuals with obesity, regardless of diabetes status. Furthermore, TLR3/TLR7/IRAK1 and TLR3/TLR9 were identified as independent predictors of AT SRA1 expression in individuals with obesity and T2D, respectively. Overall, our data demonstrate a direct association between the AT SRA1 expression and the TLRs together with their downstream signaling partners and IRFs in individuals with obesity and/or T2D.
Identifiants
pubmed: 36552771
pii: cells11244007
doi: 10.3390/cells11244007
pmc: PMC9776802
pii:
doi:
Substances chimiques
Interferon Regulatory Factors
0
Myeloid Differentiation Factor 88
0
NF-kappa B
0
steroid receptor RNA activator
0
Toll-Like Receptor 3
0
Toll-Like Receptor 9
0
Toll-Like Receptors
0
steroid receptor RNA activator, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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