The impact of aerobic exercise timing on BMAL1 protein expression and antioxidant responses in skeletal muscle of mice

Abstract

It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.

Keywords:

• Exercise timing
• BMAL1
• NRF2-mediated antioxidant responses
• skeletal muscle

Authors’ contributions

The experiment was designed by Ying Zhang and Lei Xu. Experiments were performed by Lei Xu, Jie Jia, Jingjing Yu and Shudan Miao; Data analysis and original manuscript writing were done by Lei Xu; Ying Zhang edited and revised manuscript. The published version of the manuscript has been read and approved by all authors.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

Data supporting the findings of this study are available from the corresponding author (YZ) upon reasonable request.

Additional information

Funding

The research was funded by National Natural Science Foundation of China (grant number: 32071168)