Inhibition of cardiac glucose uptake by protein acetylation, a new paradigm in diabetic cardiomyopathy
(2025)
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- Abstract
- Metabolic flexibility is essential for optimal cardiac function and is among the first alterations observed in diabetic cardiomyopathy, contributing to heart failure development. To better understand the mechanisms driving the onset of this pathology, we investigated the impact of lipid overload on cardiac metabolism. We show that excess fatty acids triggers a global rise in protein acetylation which interferes with the translocation of the transporter GLUT4 to the plasma membrane and reduces glucose uptake in cardiomyocytes. We then demonstrated that α-tubulin acetylation on lysine 40, which is elevated in hearts from high-fat diet-fed mice, negatively regulates cardiac glucose uptake. Finally, reducing α-tubulin acetylation revealed a sex-specific response in a diabetic model, with male mice developing a more severe form of diabetic cardiomyopathy, whereas females are protected.
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De Loof, M. (2025). Inhibition of cardiac glucose uptake by protein acetylation, a new paradigm in diabetic cardiomyopathy.