Abstract
OBJECTIVES: 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. CONCLUSIONS: 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.