What is the clinical evidence from this study?

Study design: Other. Population: exercise induced cardiovascular remodeling. Intervention: Dapagliflozin and exercise vs. controls. Primary outcome: cardiac morphology, sarcomeric function, and proteomic alterations.

What question did this study set out to answer?

This research aims to understand how dapagliflozin and exercise together affect heart structure and function in rats.

June 12, 2026Open Access

Interaction of dapagliflozin and exercise in a small animal model: functional, sarcomeric, and proteomic insights

Key Result

Dapagliflozin combined with 12 weeks of exercise in male rats enhanced systolic and mechanoenergetic response without affecting exercise-induced physiological myocardial hypertrophy.

Key Points

This research aims to understand how dapagliflozin and exercise together affect heart structure and function in rats.
Male Wistar rats were divided into four groups: controls, exercised, Dapa-treated, and exercised+Dapa.
Rats underwent 12 weeks of swim training with daily dapagliflozin administration (1 mg/kg).
Left ventricular function was analyzed via echocardiography, cardiomyocyte force generation, and proteomic profiling.
Exercise improved physiological hypertrophy and systolic function without affecting heart mass.
Combined exercise and dapagliflozin treatment enhanced contractility and force generation in cardiomyocytes.
Proteomics identified significant changes in proteins related to metabolism, redox regulation, and cardiovascular signaling.

Structured PICO

Does dapagliflozin combined with exercise improve cardiac morphology and sarcomeric function in a rat model of exercise-induced cardiovascular remodeling?

Population

Male Wistar rats assigned to control, exercise, dapagliflozin, or combined groups for 12 weeks.

Intervention

Dapagliflozin (1 mg/kg daily) combined with 12 weeks of swim training

Comparator

Controls (no exercise, no dapagliflozin), exercise alone, and dapagliflozin alone

Outcome

Cardiac morphology, sarcomeric function, and proteomic alterationssurrogate

Dapagliflozin and exercise induce distinct but complementary molecular adaptations that synergistically enhance systolic function and sarcomeric performance in a rat model.

Abstract

Abstract Introduction Regular exercise training acts as a cardiovascular polypill, inducing physiological myocardial hypertrophy and improved performance. Sodium-glucose transport 2 inhibitor (SGLT2i) dapagliflozin (Dapa) is a key therapy for both systolic and diastolic heart failure, but its interaction with exercise-induced remodeling remains unclear. We aimed to investigate the combined effects of Dapa and exercise on cardiac morphology, sarcomeric function, and proteomic alterations in a previously well- established rat model of exercise induced cardiovascular remodeling. Methods Male Wistar rats were assigned to four groups: controls (CoCo), exercised (ExCo), Dapa-treated (CoDa), and exercised+Dapa (ExDa). Animals underwent 12 weeks of swim training; Dapa was given daily (1 mg/kg). Echocardiography and pressure–volume analysis evaluated left ventricular morphology and function, respectively. Permeabilized cardiomyocytes were investigated for sarcomeric force generation and troponin I (TnI) phosphorylation. Left ventricular proteomics characterized molecular alterations. Results Exercise induced relevant physiological hypertrophy, while dapagliflozin did not influence myocardial mass (post-mortem heart weight CoCo 1.19±0.04g, ExCo: 1.43±0.05g, CoDa: 1.22±0.04g, CoEx: 1.45±0.05g). Both improved systolic performance, load-independent contractility, and maximal cardiomyocyte force, with the combined group (ExDa) showing the most enhanced function. Total and Ser22/23 TnI phosphorylation decreased with both interventions. Thr144 hypophosphorylation was exercise-specific and accordingly, Ca-sensitivity increased only with exercise. Proteomics revealed 260 proteins altered by exercise and 180 by Dapa, with 56 overlapping. Shared adaptations involved mitochondrial metabolism (Gys1, Fdx1, Map1), redox regulation (Catalase), angiogenesis (Fgf1), and fibrosis-related signaling (Lgals3, Prmt1). Conclusions Dapagliflozin has not been associated with the hypertrophic response of the heart, which was improved mostly through exercise. The combined treatment has resulted in enchanced systolic and mechanoenergetic response. On a molecular level dapagliflozion and exercise induce mostly distinct but several complementary adaptations converging on contractile, metabolic, and mitochondrial pathways. The improved systolic function and sarcomeric performance suggests synergistic mechanisms of these two treatments in the athlete’s heart.