Low-Intensity Pulsed Ultrasound (LIPUS) Mitigates Exercise-Induced Myocardial Fatigue by Optimizing Glucose Oxidation Via the Aldolase/AMPK/PDH Signaling Axis.

BACKGROUND

Myocardial energy deficiency is a key bottleneck limiting exercise endurance. Low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive metabolic regulator. This study investigates whether LIPUS can activate glucose-centric pathways to alleviate exercise-induced myocardial fatigue.

METHODS

Sprague-Dawley rats were subjected to a 4-week exhaustive swimming protocol. LIPUS (1 MHz, 30 mW/cm², 20% duty cycle) was administered precordially for 30 min/day. We assessed exercise tolerance, cardiac injury markers (cTnI, NT-proBNP), mitochondrial ultrastructure, and metabolic flux. The activation of the Aldolase/AMPK/PDH axis was evaluated via Western blot and qPCR.

RESULTS

LIPUS treatment significantly prolonged exhaustive swimming time and reduced serum injury markers. Ultrastructural analysis revealed preserved mitochondrial cristae and myofiber alignment in LIPUS-treated hearts. Mechanistically, LIPUS promoted a metabolic switch from anaerobic glycolysis to efficient glucose aerobic oxidation by upregulating Aldolase and p-AMPK while reducing inhibitory PDH phosphorylation. Mitochondrial TCA cycle and respiratory chain activities (Complexes I-IV) were systematically restored.

CONCLUSIONS

LIPUS enhances myocardial glucose oxidation efficiency and exercise endurance by activating the Aldolase/AMPK/PDH signaling axis. These findings highlight LIPUS as a promising non-pharmacological strategy for exercise-induced cardioprotection.