Functional Impact of Alternative Metabolic Substrates in Failing Human Cardiomyocytes

JACC Basic Transl Sci. 2023 Sep 20;9(1):1-15. doi: 10.1016/j.jacbts.2023.07.009. eCollection 2024 Jan.

Abstract

Recent studies suggest that metabolic dysregulation in patients with heart failure might contribute to myocardial contractile dysfunction. To understand the correlation between function and energy metabolism, we studied the impact of different fuel substrates on human nonfailing or failing cardiomyocytes. Consistent with the concept of metabolic flexibility, nonfailing myocytes exhibited excellent contractility in all fuels provided. However, impaired contractility was observed in failing myocytes when carbohydrates alone were used but was improved when additional substrates were added. This study demonstrates the functional significance of fuel utilization shifts in failing human cardiomyocytes.

Keywords: carbohydrates, contractility; free fatty acids; heart failure; metabolic flexibility; metabolic fuel utilization; tissue metabolites.