Metabolism of fructose in the heart favors glycerate production and is linked to cardiac dysfunction in diabetes.

Authors

Marco Annandale, Dominic Lachance, Isabelle F Robillard, George Guo, Xun Li, Parisa Koutsifeli, Lorna J Daniels, Erica Zarate, Angus C Grey, Lea M D Delbridge, Matthieu Ruiz, Christine Des Rosiers, Kimberley M Mellor

Published in

Journal of molecular and cellular cardiology. Aug 08, 2026. Epub Aug 08, 2026.

Abstract

Increased cardiac risk in diabetes has been linked to disturbances in myocardial metabolism. Circulating and cardiac fructose levels are elevated in diabetes but the relationship between fructose and cardiac pathology is unclear. The goal of this study was to assess myocardial capacity for fructose metabolism and evaluate the time-course of cardiac fructose accumulation relative to the emergence of cardiac functional impairment in diabetic rats. Cardiac capability for fructose metabolism to support function was demonstrated in ex vivo working mouse hearts perfused with 11 mM fructose. Using isotope-labeled fructose [U¹³C], we observed ¹³C enrichment into downstream metabolites glyceraldehyde, glycerate, pyruvate, lactate, and mitochondrial acetyl-CoA in perfused working mouse hearts. Metabolite profiling demonstrated that relative to glucose, myocardial fructose metabolism favored glycerate production. In diabetic rats (streptozotocin, 55 mg/kg), cardiac fructose elevation was evident prior to the onset of cardiac dysfunction. This study provides proof-of-principle evidence that fructose metabolism is operational in the working heart and identifies key fructose-derived metabolites. The finding that cardiac fructose elevation precedes functional impairment supports the contention that fructose may be an early instigator of diabetic cardiomyopathy and further investigation is now warranted. NEW AND NOTEWORTHY (<75 WORDS): Circulating and cardiac fructose levels are elevated in diabetes but the relationship between fructose and cardiac pathology is unclear. This study provides proof-of-principle evidence that fructose metabolism is operational in the working heart and identifies that cardiac fructose metabolism favors production of glycerate. In diabetes, cardiac fructose elevation precedes functional impairment supporting the contention that fructose may be an early instigator of diabetic cardiomyopathy.

PMID:
42570789
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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