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Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy

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Abstract

Metabolic cardiomyopathy is an emerging cause of heart failure in patients with obesity, insulin resistance, and diabetes. It is characterized by impaired myocardial metabolic flexibility, intramyocardial triglyceride accumulation, and lipotoxic damage in association with structural and functional alterations of the heart, unrelated to hypertension, coronary artery disease, and other cardiovascular diseases. Oxidative stress plays an important role in the development and progression of metabolic cardiomyopathy. Mitochondria are the most significant sources of reactive oxygen species (ROS) in cardiomyocytes. Disturbances in myocardial substrate metabolism induce mitochondrial adaptation and dysfunction, manifested as a mismatch between mitochondrial fatty acid oxidation and the electron transport chain (ETC) activity, which facilitates ROS production within the ETC components. In addition, non-ETC sources of mitochondrial ROS, such as β-oxidation of fatty acids, may also produce a considerable quantity of ROS in metabolic cardiomyopathy. Augmented ROS production in cardiomyocytes can induce a variety of effects, including the programming of myocardial energy substrate metabolism, modulation of metabolic inflammation, redox modification of ion channels and transporters, and cardiomyocyte apoptosis, ultimately leading to the structural and functional alterations of the heart. Based on the above mechanistic views, the present review summarizes the current understanding of the mechanisms underlying metabolic cardiomyopathy, focusing on the role of oxidative stress.

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Funding

This work was supported by grants from the Hubei Province Innovation Platform Construction Project (20204201117303072238), Wuhan Science and Technology Planning Project (2020021105012439), the National Science Foundation of China (82000386, 81870171), and the Excellent Doctoral Program of Zhongnan Hospital of Wuhan University (ZNYB2019001).

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  1. Ze Chen and Zhao-Xia Jin contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China

    Ze Chen, Ke-Qiong Deng & Zhibing Lu

  2. Department of Cardiovascular, Huanggang Central Hospital of Yangtze University, Huanggang, China

    Zhao-Xia Jin & Huo-Ping Li

  3. Institute of Model Animal, Wuhan University, Wuhan, China

    Ze Chen, Jingjing Cai, Ke-Qiong Deng, Yan-Xiao Ji, Fang Lei & Hongliang Li

  4. Department of Cardiology, Central South University, The Third Xiangya Hospital, Changsha, China

    Jingjing Cai

  5. Northfield Mount Hermon School, Gill, MA, 01354, USA

    Ruyan Li

  6. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China

    Hongliang Li

  7. Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China

    Yan-Xiao Ji & Hongliang Li

  8. Huanggang Institute of Translational Medicine, Huanggang, China

    Zhao-Xia Jin, Huo-Ping Li & Hongliang Li

  9. School of Basic Medical Science, Wuhan University, Wuhan, China

    Yan-Xiao Ji, Fang Lei & Hongliang Li

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  1. Ze Chen
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Contributions

All authors contributed toward this work. Conceptualization: Huo-Ping Li, Zhibing Lu, and Hongliang Li; literature search and analysis: Ze Chen, Zhao-Xia Jin, Ruyan Li, Ke-Qiong Deng, Yan-Xiao Ji, and Fang Lei; writing of the first draft of the manuscript: Ze Chen and Zhao-Xia Jin; review and editing: Jingjing Cai, Ruyan Li, Huo-Ping Li, Zhibing Lu, and Hongliang Li. All authors read and approved the final manuscript.

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Correspondence to Huo-Ping Li, Zhibing Lu or Hongliang Li.

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Chen, Z., Jin, ZX., Cai, J. et al. Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy. J Mol Med 100, 1721–1739 (2022). https://doi.org/10.1007/s00109-022-02269-1

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