Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventri...
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De Gruyter
2024-12-01
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Online Access: | https://doi.org/10.1515/biol-2022-0974 |
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author | Wu Yanxia Jiang Wanxiang Wang Junlong Xie Guoqing Sun Yan Yang Jinliang |
author_facet | Wu Yanxia Jiang Wanxiang Wang Junlong Xie Guoqing Sun Yan Yang Jinliang |
author_sort | Wu Yanxia |
collection | DOAJ |
description | In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM. |
format | Article |
id | doaj-art-be1e1f12883448c9b7a2e7c9c8477aad |
institution | Kabale University |
issn | 2391-5412 |
language | English |
publishDate | 2024-12-01 |
publisher | De Gruyter |
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spelling | doaj-art-be1e1f12883448c9b7a2e7c9c8477aad2025-01-20T11:08:13ZengDe GruyterOpen Life Sciences2391-54122024-12-01191101788710.1515/biol-2022-0974Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysisWu Yanxia0Jiang Wanxiang1Wang Junlong2Xie Guoqing3Sun Yan4Yang Jinliang5State/National Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, 610000, P. R. ChinaSichuan Greentech Bioscience Co., Ltd., Meishan, Sichuan, 620010, P. R. ChinaSichuan Greentech Bioscience Co., Ltd., Meishan, Sichuan, 620010, P. R. ChinaSichuan Greentech Bioscience Co., Ltd., Meishan, Sichuan, 620010, P. R. ChinaSichuan Greentech Bioscience Co., Ltd., Meishan, Sichuan, 620010, P. R. ChinaState/National Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, 610000, P. R. ChinaIn this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated. Furthermore, the study identified the transcription factor Gata3 as a predicted negative regulator of the gene encoding the key enzyme for BCAA degradation. These findings suggest that the disruption of BCAA degradation is a critical characteristic of diabetic myocardial damage and indicate a potential role for Gata3 in the dysregulation of BCAA metabolism in the context of DCM.https://doi.org/10.1515/biol-2022-0974diabetic cardiomyopathymulti-omicsamino acid metabolismbranched-chain amino acids |
spellingShingle | Wu Yanxia Jiang Wanxiang Wang Junlong Xie Guoqing Sun Yan Yang Jinliang Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis Open Life Sciences diabetic cardiomyopathy multi-omics amino acid metabolism branched-chain amino acids |
title | Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
title_full | Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
title_fullStr | Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
title_full_unstemmed | Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
title_short | Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
title_sort | disruption of bcaa degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis |
topic | diabetic cardiomyopathy multi-omics amino acid metabolism branched-chain amino acids |
url | https://doi.org/10.1515/biol-2022-0974 |
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