The role of glucose metabolic reprogramming in myocarditis and advances in therapeutic strategies

TL;DR

This paper reviews how changes in glucose metabolism contribute to myocarditis and explores new treatment strategies targeting these metabolic shifts.

Contribution

The paper provides a comprehensive overview of glucose metabolic reprogramming in myocarditis and its therapeutic implications.

Findings

Myocarditis is marked by a metabolic shift toward aerobic glycolysis, leading to inflammation and heart dysfunction.

Key regulatory mechanisms include the HIF-1α/mTOR axis and the Nrf2-mediated pentose phosphate pathway.

Multiomics technologies may enable precise metabolic interventions for treating myocarditis.

Abstract

Myocarditis is a heterogeneous inflammatory heart disease most commonly triggered by viral infections, such as Coxsackievirus B3, and may progress to dilated cardiomyopathy and heart failure. Growing evidence highlights the pivotal role of glucose metabolic reprogramming in cardiomyocytes and infiltrating immune cells during the initiation and progression of myocarditis. Under physiological conditions, the adult heart primarily relies on fatty acid β-oxidation for energy production, with glucose oxidation serving a supplementary role. In contrast, myocarditis is characterized by a metabolic shift from oxidative phosphorylation toward enhanced aerobic glycolysis, known as the Warburg effect. This shift results in reduced ATP efficiency, lactate accumulation, excessive reactive oxygen species production, and amplification of inflammatory responses, thereby establishing a self-sustaining immunometabolic vicious cycle. This review summarizes glucose metabolism in the normal heart and highlights the features and regulatory mechanisms of glucose metabolic reprogramming in myocarditis, including the hypoxia-inducible factor-1α/mammalian target of rapamycin axis, nuclear factor erythroid 2-related factor 2-mediated pentose phosphate pathway, immune-responsive gene 1/itaconate axis, and phosphoglycerate kinase 1. Emerging therapeutic strategies targeting glucose metabolism are discussed, as well as current challenges in clinical translation. Advances in multiomics technologies may facilitate the development of precise metabolic interventions for myocarditis.

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