Moderate Treadmill Training Induces Limited Effects on Quadriceps Muscle Hypertrophy in Mice Exposed to Cigarette Smoke Involving Metalloproteinase 2

Abstract

Background

Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, cross-sectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS.

Methods

Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks.

Results

The CS exposure did not change CSA compared to the control group (p>0.05), but minor fibers in the frequency distribution (<1000 µm²) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke+exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001).

Conclusion

Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions.

Keywords:

• physical exercise
• chronic obstructive pulmonary disease
• MMP-2
• inflammation

Data Sharing Statement

The de-identified data sets generated during the study are available from the corresponding author.

Ethics Approval

The present study was approved by the Animal Research Ethics Committee of the University of Sao Paulo (protocol number: CAPpesq/025/10). The research has been carried out in accordance with the Guide for care and use of laboratory animals and international principles for research involving animals (ARRIVE 2.0).

Acknowledgments

This project was supported by Sao Paulo Research Foundation (FAPESP) Grant: 2012/15165-2, by Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) and by DPI/DPG n. 01/2021. We also thank Carolina Pinho for the grammar English review and Capes by fellowship research of Ph.D. at Gracielle Vieira Ramos. JLQD has a Research Scholarship in Physical Therapy (Tier 2) from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Process numbers: 312136/2018-8).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.