High-intensity interval training alleviates COPD-induced gastrocnemius muscle dysfunction via the BRD4/PGC-1α axis through restoring mitochondrial function and oxidative fiber composition.

Journal of muscle research and cell motility 2026

Zhu C, Peng W, Yang L, Zhang W

Abstract

UNLABELLED: Skeletal muscle dysfunction (SMD) associated with Chronic obstructive pulmonary disease (COPD), characterized by muscle atrophy and altered fiber type distribution. High-intensity interval training (HIIT) is increasingly used clinically to improve cardiopulmonary and exercise functions in COPD patients, yet robust scientific evidence and exploration of its molecular mechanisms remain limited. In this research, bioinformatics analysis of GSE datasets revealed the differentially expressed genes in the gastrocnemius muscle tissues with COPD preliminarily. COPD rat models were established using cigarette smoke exposure. Cigarette smoke extract (CSE)-induced L6 myoblasts were used as cell models. It was found that BRD4 and PGC-1α were both significantly downregulated in the gastrocnemius muscle tissues with COPD and show a certain correlation. In vitro, BRD4 overexpression could restore PGC-1α levels and attenuate mitochondrial damage of L6 myoblasts caused by CSE treatment. HIIT significantly improved pulmonary function, muscle strength, and oxidative fiber composition in COPD rats by restoring the BRD4/PGC-1α axis and mitochondrial function, but the BET bromodomain inhibitor JQ1 could partially reverse the positive effects of HIIT. These findings not only provides some scientific evidence for the beneficial effects of HIIT on gastrocnemius muscle dysfunction caused by COPD but also suggest that the BRD4/PGC-1α axis plays functional roles in mediating the beneficial effects of HIIT on COPD-induced muscle dysfunction, highlighting its potential as a therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10974-026-09723-4.

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