VEGA 2/0159/26

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Evaluating anti-obesity interventions to reverse obesity-induced cardiac disease in female rats

Principal Investigator: Iuliia Baglaeva

Duration: 1/2026 – 12/2029
Coordinating Organization: Biomedical Research Center of SAS, Institute of Experimental Endocrinology

Annotation

Obesity in women increases the risk of type 2 diabetes and diminishes hormonal cardioprotection, yet
female-specific myocardial responses to obesity and its treatment remain poorly understood. This study will investigate cardiac dysfunction in obese female Zucker Diabetic Fatty (ZDF) rats undergoing three anti-obesity interventions: structured exercise, B-vitamin metabolic therapy, and semaglutide treatment. We will assess how each intervention affects cardiac function and correlate these changes with myocardial morphology, cardiomyocyte ultrastructure, contractility, and protein expression in young adult rats. Age-specific cohorts will be evaluated for diabetic status and cardiac performance. Finally, the most effective intervention will be applied preventively in the youngest group showing early cardiac impairment. This work will clarify mechanisms of obesity-induced myocardial dysfunction in females and support the development of sex-specific therapeutic strategies.

Keywords

cardiac remodeling; cardiac hypertrophy; calcium signaling; cardiomyocyte cyto-architecture; exercise training; metabolic syndrome; metabolic therapy; semaglutide; obesity; female ZDF rats

Objectives

This study aims to determine the comparative and temporal effects of three therapeutic strategies— exercise training, B-vitamin–based metabolic therapy and semaglutide administration—on obesity-induced cardiac remodeling in female ZDF rats, a model of metabolic syndrome. The primary objective is to identify which intervention most effectively mitigates early myocardial dysfunction, with a focus on subcellular structural and calcium-handling adaptations.

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