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Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure

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Abstract

The heart is the most energy-demanding organ throughout the whole body. Perturbations or failure in energy metabolism contributes to heart failure (HF), which represents the advanced stage of various heart diseases. The poor prognosis and huge economic burden associated with HF underscore the high unmet need to explore novel therapies targeting metabolic modulators beyond conventional approaches focused on neurohormonal and hemodynamic regulators. Emerging evidence suggests that alterations in metabolic substrate reliance, metabolic pathways, metabolic by-products, and energy production collectively regulate the occurrence and progression of HF. In this review, we provide an overview of cardiac metabolic remodeling, encompassing the utilization of free fatty acids, glucose metabolism, ketone bodies, and branched-chain amino acids both in the physiological condition and heart failure. Most importantly, the latest advances in pharmacological interventions are discussed as a promising therapeutic approach to restore cardiac function, drawing insights from recent basic research, preclinical and clinical studies.

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Abbreviations

BCAA:

Branched-chain amino acids

CoQ:

Coenzyme Q10

CPT1:

Carnitine palmitoyl transferase-1

DCA:

Dichloroacetate

ETC:

Electron transport chain

FFA:

Free fatty acids

GLP-1:

Glucagon-like peptide-1

GLUT:

Glucose transporter

GRK2:

G protein-coupled receptor kinase 2

MCD:

Malonyl CoA decarboxylase

NR:

Nicotinamide riboside

PDH:

Glucose dehydrogenase enzyme

PDK:

Pyruvate dehydrogenase kinases

PPAR:

Peroxisome proliferator-activated receptor

ROS:

Reactive oxygen species

SGLT-2:

Sodium-glucose cotransporter-2

SIRT3:

Sirtuin family member sirtuin-3

TCA:

Tricarboxylic acid

β-OHB:

β-Hydroxybutyrate

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Acknowledgements

Figures were created in Biorender.

Funding

This work was supported by Zhejiang Provincial Natural Science Foundation (LR21H020001 to HM), National Natural Science Foundation of China (82270386 to HM, 82070251 to MX), and Zhejiang Provincial Medical and Health Technology Project (2023RC020 to SY).

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Authors and Affiliations

  1. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University; State Key Laboratory of Transvascular Implantation Devices; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, Zhejiang, 310009, China

    Simin Meng, Yi Yu, Shiyu Zhu, Mengjia Shi, Meixiang Xiang & Hong Ma

  2. Department of Anesthesiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, China

    Shuo Yu

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  1. Simin Meng
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  2. Yi Yu
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  3. Shuo Yu
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  4. Shiyu Zhu
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  5. Mengjia Shi
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  6. Meixiang Xiang
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  7. Hong Ma
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Contributions

SM, YY, and SY wrote the manuscript; SM and MS prepared the figures; SY and SZ contributed to the discussion of the content; HM and MX conceived and revised the manuscript. All authors have read and agreed to the final version of the manuscript.

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Correspondence to Meixiang Xiang or Hong Ma.

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Meng, S., Yu, Y., Yu, S. et al. Advances in Metabolic Remodeling and Intervention Strategies in Heart Failure. J. of Cardiovasc. Trans. Res. 17, 36–55 (2024). https://doi.org/10.1007/s12265-023-10443-0

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