Exercise Preconditioning Activates AMPK-ACC Signaling and Attenuates Myocardial Ischemia/Reperfusion-Induced Ferroptosis.

Authors

Yuxiang Xu, Jie Tang, Chenyang Wu, Ruizhen Li, Yifang Zhao, Mengxin Cai, Zhenjun Tian

Published in

Journal of cardiovascular translational research. Volume 19. Issue 1. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

Ferroptosis critically mediates myocardial ischemia/reperfusion (I/R) injury. Exercise training confers cardioprotection, but whether it protects against I/R-induced ferroptosis and the underlying mechanisms remain unclear. In this study, C57BL/6J mice underwent six weeks of treadmill exercise preconditioning (EP) before myocardial I/R induction. Cardiac function, oxidative stress, ferroptosis markers and the phosphorylation of AMPK and ACC were assessed. In vitro, H9C2 cells were subjected to hypoxia/reoxygenation (H/R), and pharmacological modulators were used to investigate the necessity of the AMPK-ACC signaling. Results showed that EP alleviated I/R-induced cardiac dysfunction, reduced oxidative stress and iron deposition, upregulated GPX4 and SLC7A11 expression, downregulated ACSL4 expression, and enhanced the phosphorylation of AMPK and ACC. In H9C2 cells, H/R reduced ACC phosphorylation and induced ferroptosis. AMPK inhibition exacerbated H/R-induced ferroptosis, whereas AMPK activation by AICAR was protective. Critically, blocking ACC enzymatic activity attenuated AICAR's effects. These findings indicate that EP attenuates I/R-induced ferroptosis and the AMPK-ACC signaling may contribute to this protective effect.

PMID:
42565937
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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