Document Type : Original Article

Authors

¹ Department of Physical Education and Sport Sciences, SR.C., Islamic Azad university, Tehran, Iran.

² Exercise Physiology Research Center, life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

What is already known on this subject?

Regular physical activity is associated with reduced breast cancer risk, decreased recurrence rates, and improved survival outcomes in breast cancer patients. Adiponectin, through its receptor AdipR1, exerts anti-proliferative effects on breast cancer cells via AMPK-mediated pathways leading to cell cycle arrest, while obesity-related adipokine dysregulation (low adiponectin, high leptin) creates a tumor-promoting microenvironment. Exercise training modulates systemic antioxidant enzyme activities, including GPX and GR, through hormetic adaptations to exercise-induced oxidative stress. HIIT has emerged as a time-efficient exercise modality that induces superior improvements in cardiorespiratory fitness and metabolic health compared to traditional moderate-intensity training, with emerging evidence suggesting HIIT can increase serum levels of anti-cancer myokines in breast cancer patients.

What this study adds?

This study provides the first direct evidence that four weeks of HIIT significantly upregulates AdipR1 gene expression within breast tumor tissue itself, demonstrating that exercise-induced signals can penetrate the tumor microenvironment and potentially enhance cancer cell sensitivity to adiponectin's anti-proliferative effects. The robust upregulation of intratumoral AdipR1 (p<0.0001) following HIIT suggests that high-intensity exercise may be particularly effective at restoring adiponectin sensitivity and counteracting obesity-associated tumor-promoting adipokine dysregulation. Additionally, this study demonstrates that HIIT significantly reduces serum GPX levels in tumor-bearing mice, revealing a distinct antioxidant response pattern compared to traditional moderate-intensity exercise, while GR levels remained unchanged, and indicating differential regulation of glutathione system components. These findings establish HIIT as a modulator of both adipokine signaling and oxidative stress pathways in breast cancer, providing mechanistic insight into how exercise intensity may influence tumor biology through multiple convergent mechanisms.

Keywords

• Cellular & Molecular Exercise Physiology

Acknowledgements

None.

Funding

None.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest the authors declare that there is no conflict of interest in the present research.

Ethical approval All experimental procedures were conducted in strict accordance with the ethical guidelines for the care and use of laboratory animals. The study protocol was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Baqiyatallah University of Medical Sciences and Islamic Azad University, Tehran, Iran (ethical code: IR.IAU.SRB. REC.1403,527). Furthermore, the research complied with the NIH Guide for the Care and Use of Laboratory Animals (8th Edition, National Academies Press, 2011) to ensure the highest standards of animal welfare. Efforts were made to minimize animal suffering and reduce the number of animals used.

Informed consent Animal study. 

Author contributions 

Conceptualization: S.N., Methodology: H.Sh., Software: M.Gh., Validation: H.A.,; Formal analysis: F.Gh.,; Investigation: H.Sh.,; Resources: S.N.,; Data curation: H.A.,; Writing - original draft: F.Gh.,; Writing–review & editing H.Sh.,; Visualization: S.N.,; Supervision: M.Gh.; Project administration: H.Sh.,.; Funding acquisition: S.N.