Aerobic exercise regulates macrophage polarization and improves insulin resistance in mice:the mediating role of miR-221-3p
LI Nan
ZHANG Liang
GUO Qiaofeng
ZHOU Yue
LIU Changjiang
Abstract：Objective To explore the role of miR-221-3p in mediating the positive effects of aerobic exercise on macrophage polarization in the adipose tissues and insulin resistance(IR).Methods Sixteen normal C57BL/6J mice and 16 mice with IR induced by high-fat diet(HFD)feeding for 12 weeks were both randomized into sedentary group and exercise group with aerobic exercise training on a treadmill(5 times per week for 8 consecutive weeks).All the mice were examined for changes in body weight,body composition,fasting blood glucose,blood lipid levels,insulin levels,miR-221-3p expression level,mRNA levels of Socs1,Tnf-α and Arg-1,and protein levels of SOCS1,JAK1,p-STAT1,and p-STAT3 in the adipose tissues,and the targeting relationship between miR-221-3p and SOCS1 was validated using dual-luciferase reporter gene assay.In RAW264.7 macrophages,the effects of transfection with miR-221-3p mimic or inhibitor on macrophage polarization were observed.Results In mice with normal feeding,aerobic exercise significantly decreased body weight,fat mass,fat percent,fasting blood glucose,serum insulin level,HOMA-IR,and TC and TG levels,and reduced miR-221-3p levels in both the plasma and the adipose tissues.The sedentary IR mice showed significantly increased miR-221-3p levels in both the plasma and adipose tissue,increased protein levels of iNOS,JAK1,and p-STAT1/STAT1,and decreased protein levels of Arg-1,SOCS1 and p-STAT3/STAT3,which were significantly reversed after aerobic exercise intervention.Dual-luciferase reporter gene assays validated the targeting relationship between miR-221-3p and SOCS1.In RAW264.7 macrophages,miR-221-3p overexpression significantly reduced Socs1 and Arg-1 mRNA expression,whereas miR-221-3p inhibition obviously promoted M2 polarization of the macrophages.Conclusion Aerobic exercise improves HFD-induced IR in mice possibly by inhibiting miR-221-3p to activate the SOCS1 and JAK/STAT signaling pathway,thereby promoting macrophage M2 polarization and alleviating chronic inflammation in the adipose tissue.
Keywords：aerobic exerciseinsulin resistancemicroRNAmacrophage polarization
Publication Date：2026-01-20
Online Publishing Date：2026-01-22(First online date of this platform, not the publication date of the document)
Pages：9( 74-82 )