Aerobic exercise improves inflammation and insulin resistance in skeletal muscle by regulating miR-221-3p via JAK/STAT signaling pathway

有氧运动通过JAK/STAT信号通路调控miR-221-3p改善骨骼肌炎症和胰岛素抵抗

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作者:Nan Li, Liang Zhang, Qiaofeng Guo, Haiyan Shi, Yanming Gan, Weiqing Wang, Xiaoying Yang, Yue Zhou

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.

Conclusion

Aerobic exercise improved chronic inflammation and IR in the skeletal muscle, with miR-221-3p as a key modulator of macrophage polarization.

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 enzyme-linked 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.

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