miR-146a regulates inflammatory cytokines and reverses high-glucose- and high-insulin-induced insulin resistance in 3T3-L1 adipocytes by targeting Traf6 through the NF-κB signaling pathway

Insulin resistance (IR) is a common feature of type 2 diabetes mellitus. Therefore, the molecular mechanism of IR in adipocytes is becoming a focal point of diabetes research. Emerging evidence suggests that miR-146a might be associated with diabetes and its related complications. However, the role of miR-146a in the development of IR remains unclear. In this study, we found that the expression of miR-146a was significantly inhibited in IR-3T3L1 adipocytes compared with that in normal 3T3-L1 adipocytes, while that of Traf6 was significantly promoted. The overexpression of miR-146a significantly inhibited the expression of Traf6, silenced the NF-kappa B signaling pathway, reduced the secretion of inflammatory cytokines, and increased glucose uptake in IR-3T3-L1 adipocytes. Traf6 overexpression had no effect on the expression of miR-146a, but partially alleviated the effect of miR-146a in adipocytes transfected with miR-146a mimic. In conclusion, we demonstrated that miR-146a silenced the NF-kappa B signaling pathway, decreased the secretion of inflammatory cytokines, and improved glucose uptake in IR-3T3-L1 adipocytes by targeting Traf6. The findings provide information regarding a potential new therapeutic strategy to control IR in adipocytes.