Work

Sirtuin signalling governs calcium homeostasis and mitochondrial function in metabolic syndrome cardiomyocytes

Year: 2026

Type: article

Abstract: Metabolic syndrome (MetS) is a major contributor to cardiovascular disease and is characterized by impaired Ca 2+ handling and mitochondrial dysfunction in cardiomyocytes. However, the upstream mechanisms linking metabolic stress to these alterations remain incompletely defined. Here, we investigated whether sirtuin signalling coordinates intracellular Ca 2+ homeostasis and mitochondrial function in a high‐sucrose diet‐induced mouse model of MetS. Male BALB/c mice were exposed to 32% sucrose for 24 weeks, followed by isolation of ventricular cardiomyocytes. MetS cardiomyocytes exhibited mitochondrial depolarization, increased reactive oxygen species production, elevated basal cytosolic Ca 2+ levels, reduced Ca 2+ transient amplitude and decreased sarcoplasmic reticulum Ca 2+ content. These alterations were associated with reduced phospholamban phosphorylation, increased CaMKII and ryanodine receptor phosphorylation and activation of pro‐apoptotic signalling. Notably, pharmacological inhibition of SIRT1 with EX527 in control cardiomyocytes recapitulated key features of the MetS phenotype, whereas SIRT1 activation with SRT1720 restored mitochondrial membrane potential, reduced reactive oxygen species production, improved Ca 2+ handling, normalized aberrant phosphorylation of Ca 2+ ‐handling proteins and attenuated apoptotic signalling. Collectively, these findings identify SIRT1 as a critical integrator of mitochondrial function and Ca 2+ homeostasis during metabolic stress, highlighting sirtuin‐dependent pathways as promising therapeutic targets in metabolic cardiomyopathy.

Source: Experimental Physiology

DOI: 10.1113/ep094062

Authors: Firat Akat, Leila Aryan, Suatnur Şık, Erkan Tuncay

Institution: Ankara University

Language: English

Topic: Sirtuins and Resveratrol in Medicine

Subfield: Geriatrics and Gerontology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,940