Obesity-induced changes in ultrastructure and calcium release of female rat cardiomyocytes are partially reversed by aerobic exercise.

Obesity is associated with an elevated risk of pathological cardiac hypertrophy, whereas exercise confers cardioprotective effects; however, the cellular mechanisms underlying these opposing influences remain incompletely defined, particularly in females. We investigated how obesity and exercise affect cardiomyocyte ultrastructure, Ca²⁺ release, and contractility in female Zucker Diabetic Fatty rats and their lean littermates. Animals were assigned at 12 weeks to sedentary or aerobic exercise-trained groups and maintained on a standard diet. By 18 weeks, obese rats exhibited increased body mass and myocardial hypertrophy in the absence of diabetes. Sedentary obese animals showed a reduced fraction of compact dyads and diminished stimulated and caffeine-induced Ca²⁺ release, while contractility remained preserved. In lean rats, exercise increased dyad density but reduced Ca²⁺ release, whereas in obese rats, exercise enhanced both dyad compactness and Ca²⁺ release. Across all groups, global cardiomyocyte ultrastructure and contractile function were similar. Type III ANOVA revealed a significant obesity × exercise interaction for dyadic structure and Ca²⁺ release. These findings demonstrate that obesity itself, independent of diabetes, triggers early dyadic remodeling and altered Ca²⁺ handling in female myocardium before detectable impairment of global cardiomyocyte structure or contractile function. Furthermore, exercise exerts beneficial effects on dyadic ultrastructure and Ca²⁺ signaling in obese animals.