BDNF contributes to the skeletal muscle anti-atrophic effect of exercise training through AMPK-PGC1α signaling in heart failure mice.

INTRODUCTION

Exercise training is a coadjuvant therapy in preventive cardiology, and it delays cardiac dysfunction and exercise intolerance in heart failure (HF). However, the mechanisms underlying muscle function improvement and cardioprotection are poorly understood. In this study, we tested whether exercise training would counteract skeletal muscle atrophy via activation of the BDNF pathway in myocardial infarction (MI)-induced HF mice.

MATERIAL AND METHODS

A cohort of male Sham-operated and MI mice were assigned into 8-week moderate exercise training, and untrained counterparters were used as control. Exercise capacity, plasma norepinephrine (NE) level, heart rate (HR), fractional shortening (FS) and ejection fraction (EF) were measured. The protein expression of BDNF, p-TrkB, p-AMPK and PGC1α were analyzed by Western blot.

RESULTS

Compared with the Sham-operated mice, MI mice displayed reduced total distance run and elevated plasma NE level (both < 0.05). Exercise training significantly improved distance run and plasma NE levels in HF mice (both < 0.05). Significantly increased HR, decreased FS and EF were observed in the MI group as compared to the Sham-operated group, and exercise training prevent the hemodynamic status and systolic dysfunction in MI mice (all < 0.05). The expression of BDNF, p-TrkB, p-AMPK and PGC1α were significantly decreased in the skeletal muscle from MI compared to Sham-operated mice, which were significantly increased by exercise training (all < 0.05). In addition, BDNF siRNA markedly decreased the protein level of p-AMPK and PGC1α in C2C12 myoblasts.

CONCLUSIONS

Taken together, our data provide evidence for exercise training may counteract HF-induced muscle atrophy through induced activation of BDNF pathway.