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Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.

Yanxia Wu | Wanxiang Jiang | Junlong Wang | Guoqing Xie | Yan Sun | Jinliang Yang
Open life sciences | 2024

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.

Pubmed ID: 39822378

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