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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
JCI insight - 7(2022), 19 vom: 10. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bapat, Aneesh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.01.2023 Date Revised 23.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.160885 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345165276 |
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| 100 | 1 | |a Bapat, Aneesh |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic inhibition of serum glucocorticoid kinase 1 prevents obesity-related atrial fibrillation |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Arrhythmias | |
| 650 | 4 | |a Cardiology | |
| 650 | 4 | |a Metabolism | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Sodium |2 NLM | |
| 650 | 7 | |a 9NEZ333N27 |2 NLM | |
| 650 | 7 | |a serum-glucocorticoid regulated kinase |2 NLM | |
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| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
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| 700 | 1 | |a Li, Guoping |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Yeri, Ashish |e verfasserin |4 aut | |
| 700 | 1 | |a Hulsmans, Maarten |e verfasserin |4 aut | |
| 700 | 1 | |a Grune, Jana |e verfasserin |4 aut | |
| 700 | 1 | |a Yamazoe, Masahiro |e verfasserin |4 aut | |
| 700 | 1 | |a Schloss, Maximilian J |e verfasserin |4 aut | |
| 700 | 1 | |a Iwamoto, Yoshiko |e verfasserin |4 aut | |
| 700 | 1 | |a Tedeschi, Justin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Nahrendorf, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenzweig, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Ellinor, Patrick T |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Saumya |e verfasserin |4 aut | |
| 700 | 1 | |a Milan, David |e verfasserin |4 aut | |
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