miR-330-5p/Tim-3 axis regulates macrophage M2 polarization and insulin resistance in diabetes mice

Obesity is associated with a state of low-grade inflammatory response in adipose tissue, and contributes to the development of type 2 diabetes. Immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Therefore, adipose tissue promotes macrophage infiltration, resulting in local inflammation and insulin resistance. Tim-3 negatively regulates IFN-γ secretion and influences the ability to induce T cell tolerance in diabetes. MicroRNA contributes to the development of immunological tolerance and involves in macrophage polarization. However, the potential of Tim-3 to regulate macrophage polarization and the related microRNA has not been reported. In this experiment, 8-week-old C57BL/6 mice were fed a high-fat diet for 8 weeks. The adipose tissue macrophages were isolated, miR-330-5p and Tim-3 levels, and M1/M2 polarization were analyzed. In addition, insulin tolerance tests was detected. The results demonstrated that miR-330-5p levels increased but Tim-3 levels decreased, leading to M1 polarization and insulin tolerance in diabetes mice. In addition, inhibition of miR-330-5p enhanced Tim-3 levels, leading to M2 polarization and insulin tolerance attenuation in diabetes mice. Furthermore, we detected the inverse relationship between miR-330-5p and Tim-3. We found that Tim-3 mRNA contained conserved miR-330-5p binding sites in its 3'UTR, and miR-330-5p could directly regulate Tim-3 expression through these 3'UTR sites. Our study demonstrated that miR-330-5p served as a regulator of the M2 polarization and miR-330-5p/Tim-3 axis potentially down-regulated insulin resistance in diabetes, probably through enhancing the M2 polarization of macrophage.