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Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity

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 metabo...

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Autores principales: Kochumon, Shihab, Arefanian, Hossein, Sindhu, Sardar, Thomas, Reeby, Jacob, Texy, Al-Sayyar, Amnah, Shenouda, Steve, Al-Rashed, Fatema, Koistinen, Heikki A., Al-Mulla, Fahd, Tuomilehto, Jaakko, Ahmad, Rasheed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776802/
https://www.ncbi.nlm.nih.gov/pubmed/36552771
http://dx.doi.org/10.3390/cells11244007
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author Kochumon, Shihab
Arefanian, Hossein
Sindhu, Sardar
Thomas, Reeby
Jacob, Texy
Al-Sayyar, Amnah
Shenouda, Steve
Al-Rashed, Fatema
Koistinen, Heikki A.
Al-Mulla, Fahd
Tuomilehto, Jaakko
Ahmad, Rasheed
author_facet Kochumon, Shihab
Arefanian, Hossein
Sindhu, Sardar
Thomas, Reeby
Jacob, Texy
Al-Sayyar, Amnah
Shenouda, Steve
Al-Rashed, Fatema
Koistinen, Heikki A.
Al-Mulla, Fahd
Tuomilehto, Jaakko
Ahmad, Rasheed
author_sort Kochumon, Shihab
collection PubMed
description 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.
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spelling pubmed-97768022022-12-23 Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity Kochumon, Shihab Arefanian, Hossein Sindhu, Sardar Thomas, Reeby Jacob, Texy Al-Sayyar, Amnah Shenouda, Steve Al-Rashed, Fatema Koistinen, Heikki A. Al-Mulla, Fahd Tuomilehto, Jaakko Ahmad, Rasheed Cells Article 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. MDPI 2022-12-11 /pmc/articles/PMC9776802/ /pubmed/36552771 http://dx.doi.org/10.3390/cells11244007 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kochumon, Shihab
Arefanian, Hossein
Sindhu, Sardar
Thomas, Reeby
Jacob, Texy
Al-Sayyar, Amnah
Shenouda, Steve
Al-Rashed, Fatema
Koistinen, Heikki A.
Al-Mulla, Fahd
Tuomilehto, Jaakko
Ahmad, Rasheed
Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title_full Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title_fullStr Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title_full_unstemmed Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title_short Expression of Steroid Receptor RNA Activator 1 (SRA1) in the Adipose Tissue Is Associated with TLRs and IRFs in Diabesity
title_sort expression of steroid receptor rna activator 1 (sra1) in the adipose tissue is associated with tlrs and irfs in diabesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9776802/
https://www.ncbi.nlm.nih.gov/pubmed/36552771
http://dx.doi.org/10.3390/cells11244007
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