Effects of High-Intensity Interval Training and Semaglutide on Cardiac IL-6 and TNF-α Expression in High-Fat Diet-Fed Mice

Document Type : Research Paper

Authors

Department of Sport Sciences, Faculty of Humanities, University of Kashan, Kashan, Iran

10.22080/jaep.2026.30826.2242

Abstract

Background and Objective: A high-fat diet leads to metabolic and cardiovascular complications through inflammatory mechanisms. This study aimed to investigate the effects of high-intensity interval training (HIIT) and semaglutide, separately and in combination, on cardiac TNF-α and IL-6 levels in rats fed a high-fat diet (HFD).
Materials and Methods:  Thirty male C57BL/6J mice were randomly assigned to five groups: normal diet, HFD, HFD + HIIT, HFD + semaglutide, and HFD + HIIT + semaglutide. The interventions were applied over eight weeks, after which cardiac tissue samples were collected. The expression levels of TNF-α and IL-6 were measured, and histological assessments were performed to evaluate structural changes.
Results: The HFD group showed a significant increase in cardiac TNF-α and IL-6 levels compared to the control group. Both HIIT and semaglutide interventions independently reduced these inflammatory markers (p<0/05). However, the combined intervention group exhibited the most pronounced reduction in TNF-α and IL-6, indicating a synergistic effect (p<0/05). Histological analyses supported these findings, revealing improved cardiac structure, particularly in the combined group.
Conclusion: The results suggest that integrating HIIT with semaglutide provides the most effective strategy for reducing cardiac inflammation induced by a high-fat diet. These findings highlight the importance of exercise-based interventions and introduce semaglutide as a promising cardioprotective agent with anti-inflammatory properties. Future studies are recommended to investigate the long-term effects of this combined approach in human models.

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