有氧运动通过调控miR-221-3p介导的脂肪组织巨噬细胞极化改善小鼠胰岛素抵抗

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Abstract：ObjectiveToexplore theroleof miR-221-3pinmediating thepositiveeffectsofaerobic exerciseonmacrophage polarization intheadipose tissuesand insulinresistance（IR）.Methods Sixten normal C57BL/6Jmiceand16 mice with IR induced by high-fat diet （HFD）feding for 12 weeks wereboth randomized into sedentary groupand exercise group with aerobic exercise training onatreadmill（5 timesper weekfor8consecutive weeks）. Allthemice were examinedforchanges in bodyweightdposisngblodoeodlidvelssuinevels2-3pessonle levelsofocs1， α and Arg-1，and protein levels ofSOCS1， JAK1， p-STAT1，and p-STAT3 in the adipose tissues，and the targetingrelationshipbetweenmiR-221-3pandSOCS1was validatedusingdual-luciferasereportergeneassy.InRAW264.7 macrophages，the efectsof transfection with miR-21-3pmimicor inhibitoronmacrophage polarization wereobserved. ResultsInmiceihoraledingerobicexercisesgniicantlcreasedbodyight，ftmass，fatperentfingblood glucose，seruminsulinlevel，HOMA-IRandTCandTGlevels，andreducedmiR-221-3plevels inboththeplasmaandthe adiposetisses.ThesedentaryIRmiceshowedsignificantlyincreasedmiR-221-3plevelsinboththeplasmaandadiposetissue increased protein levelsofiNOS，JAK1，andp-STAT/STAT1nddecreased proteinlevelsofArg-1，OCS1andp-A3/ STAT3，whichweresignificantlyreversedafteraerobicexerciseintervetion.Dual-luciferasereportergeneassaysvalidatedthe targetingrelationshpbetweemiR-221-3pandSOC1.InRAW264.7macroages，miR-221-3poverexpressonsigiicantly reducedSocs1andArg-1mRNAexpression，whereasmiR-221-3pinhibitionobviouslypromotedM2polarizationof the macrophages.Conclusion Aerobic exercise improves HFD-induced IRinmicepossiblybyinhibitingmiR-21-3ptoactivate the SOCS1 and JAK/STAT signaling pathway，thereby promoting macrophage M2 polarization and aleviating chronic inflammation in the adipose tissue.

Keywords：aerobic exercise;insulin resistance;microRNA;macrophage polarization

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