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Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation

Obesity is an important risk factor for atrial fibrillation (AF), but a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned within multiple obesity-related pathways, and prior work has shown a pathologic rol...

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Autores principales: Bapat, Aneesh, Li, Guoping, Xiao, Ling, Yeri, Ashish, Hulsmans, Maarten, Grune, Jana, Yamazoe, Masahiro, Schloss, Maximilian J., Iwamoto, Yoshiko, Tedeschi, Justin, Yang, Xinyu, Nahrendorf, Matthias, Rosenzweig, Anthony, Ellinor, Patrick T., Das, Saumya, Milan, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675459/
https://www.ncbi.nlm.nih.gov/pubmed/35998035
http://dx.doi.org/10.1172/jci.insight.160885
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author Bapat, Aneesh
Li, Guoping
Xiao, Ling
Yeri, Ashish
Hulsmans, Maarten
Grune, Jana
Yamazoe, Masahiro
Schloss, Maximilian J.
Iwamoto, Yoshiko
Tedeschi, Justin
Yang, Xinyu
Nahrendorf, Matthias
Rosenzweig, Anthony
Ellinor, Patrick T.
Das, Saumya
Milan, David
author_facet Bapat, Aneesh
Li, Guoping
Xiao, Ling
Yeri, Ashish
Hulsmans, Maarten
Grune, Jana
Yamazoe, Masahiro
Schloss, Maximilian J.
Iwamoto, Yoshiko
Tedeschi, Justin
Yang, Xinyu
Nahrendorf, Matthias
Rosenzweig, Anthony
Ellinor, Patrick T.
Das, Saumya
Milan, David
author_sort Bapat, Aneesh
collection PubMed
description Obesity is an important risk factor for atrial fibrillation (AF), but a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned within multiple obesity-related pathways, and prior work has shown a pathologic role of SGK1 signaling in ventricular arrhythmias. We validated a mouse model of obesity-related AF using wild-type mice fed a high-fat diet. RNA sequencing of atrial tissue demonstrated substantial differences in gene expression, with enrichment of multiple SGK1-related pathways, and we showed upregulated of SGK1 transcription, activation, and signaling in obese atria. Mice expressing a cardiac specific dominant-negative SGK1 were protected from obesity-related AF, through effects on atrial electrophysiology, action potential characteristics, structural remodeling, inflammation, and sodium current. Overall, this study demonstrates the promise of targeting SGK1 in a mouse model of obesity-related AF.
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spelling pubmed-96754592022-11-21 Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation Bapat, Aneesh Li, Guoping Xiao, Ling Yeri, Ashish Hulsmans, Maarten Grune, Jana Yamazoe, Masahiro Schloss, Maximilian J. Iwamoto, Yoshiko Tedeschi, Justin Yang, Xinyu Nahrendorf, Matthias Rosenzweig, Anthony Ellinor, Patrick T. Das, Saumya Milan, David JCI Insight Research Article Obesity is an important risk factor for atrial fibrillation (AF), but a better mechanistic understanding of obesity-related atrial fibrillation is required. Serum glucocorticoid kinase 1 (SGK1) is a kinase positioned within multiple obesity-related pathways, and prior work has shown a pathologic role of SGK1 signaling in ventricular arrhythmias. We validated a mouse model of obesity-related AF using wild-type mice fed a high-fat diet. RNA sequencing of atrial tissue demonstrated substantial differences in gene expression, with enrichment of multiple SGK1-related pathways, and we showed upregulated of SGK1 transcription, activation, and signaling in obese atria. Mice expressing a cardiac specific dominant-negative SGK1 were protected from obesity-related AF, through effects on atrial electrophysiology, action potential characteristics, structural remodeling, inflammation, and sodium current. Overall, this study demonstrates the promise of targeting SGK1 in a mouse model of obesity-related AF. American Society for Clinical Investigation 2022-10-10 /pmc/articles/PMC9675459/ /pubmed/35998035 http://dx.doi.org/10.1172/jci.insight.160885 Text en © 2022 Bapat et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Bapat, Aneesh
Li, Guoping
Xiao, Ling
Yeri, Ashish
Hulsmans, Maarten
Grune, Jana
Yamazoe, Masahiro
Schloss, Maximilian J.
Iwamoto, Yoshiko
Tedeschi, Justin
Yang, Xinyu
Nahrendorf, Matthias
Rosenzweig, Anthony
Ellinor, Patrick T.
Das, Saumya
Milan, David
Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title_full Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title_fullStr Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title_full_unstemmed Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title_short Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
title_sort genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675459/
https://www.ncbi.nlm.nih.gov/pubmed/35998035
http://dx.doi.org/10.1172/jci.insight.160885
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