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ORIGINAL RESEARCH article
Front. Physiol.
Sec. Striated Muscle Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1534911
Aerobic Exercise Improves Inflammation and Insulin Resistance in Skeletal Muscle by regulating miR-221-3p via JAK/STAT Signaling Pathway
Provisionally accepted
Nan Li 1,2*
Liang Zhang 3
Qiaofeng Guo 2
Haiyan Shi 2 Yanming Gan 2 Weiqing Wang 2 Xiaoying Yang 4
Yue Zhou 2,5- 1 Center for Physical Education, Xi’an Jiaotong University, Xi’an, Shaanxi, China
- 2 Department of Exercise Physiology, Beijing Sport University, Beijing, China
- 3 School of Strength and Conditioning Training, Beijing Sport University, Beijing, China
- 4 National Institute of Sports Medicine, Beijing, China
- 5 Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China
Background: Exercise improves insulin sensitivity and lipid metabolism while the mechanisms remain unclear. microRNAs (miRNAs) have been linked to the development of type 2 diabetes mellitus (T2DM) and served as a potential therapeutic target. The study aimed to explore how aerobic exercise prevents chronic inflammation and insulin resistance (IR) in skeletal muscle.Methods: Fifty C57BL/6J male mice were divided into a normal (CON) or high-fat diet (HFD) for 12 weeks, followed by treadmill training for 8 weeks. Glucose levels were evaluated by glucose tolerance test, insulin tolerance test and kits. Chronic inflammatory states were evaluated by enzymelinked immunosorbent assay and immunofluorescence stain. The role of miR-221-3p was determined using miRNA sequencing and dual luciferase reporter gene assays. Metabolic alterations in skeletal muscle were investigated by Real-time PCR and western blot.Results: Aerobic exercise reduced body weight, fasting blood glucose gain, and improved insulin sensitivity. It suppressed inflammation by altering IL-1β, IL-10 levels, and macrophage polarization in the skeletal muscle. Moreover, exercise prevented chronic inflammation by diminished miR-221-3p and downstream JAK/STAT pathways. Conclusion: Aerobic exercise improved chronic inflammation and IR in the skeletal muscle, with miR-221-3p as a key modulator of macrophage polarization.
Keywords: aerobic exercise, skeletal muscle, Insulin Resistance, Macrophage polarization, MiR-221-3p
Received: 26 Nov 2024; Accepted: 06 Feb 2025.
Copyright: © 2025 Li, Zhang, Guo, Shi, Gan, Wang, Yang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Nan Li, Center for Physical Education, Xi’an Jiaotong University, Xi’an, 710049, Shaanxi, China
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