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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Main Authors: Wu Yanxia, Jiang Wanxiang, Wang Junlong, Xie Guoqing, Sun Yan, Yang Jinliang
Format: Article
Language:English
Published: De Gruyter 2024-12-01
Series:Open Life Sciences
Subjects:
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.
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institution Kabale University
issn 2391-5412
language English
publishDate 2024-12-01
publisher De Gruyter
record_format Article
series Open Life Sciences
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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