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Metabolic remodeling of substrate utilization during heart failure progression

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Abstract

Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is “an engine out of fuel” has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled.

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Funding

This study was funded by CAMS Innovation Fund for Medical Sciences (2016-I2M-1-015) and the National Natural Science Foundation of China (81670376).

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  1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital; National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), 167A Beilishi Road, Xi Cheng District, Beijing, 100037, People’s Republic of China

    Liang Chen, Jiangping Song & Shengshou Hu

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  1. Liang Chen
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  2. Jiangping Song
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Correspondence to Jiangping Song.

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Chen, L., Song, J. & Hu, S. Metabolic remodeling of substrate utilization during heart failure progression. Heart Fail Rev 24, 143–154 (2019). https://doi.org/10.1007/s10741-018-9713-0

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