Moreover, the inhibited effect of miR-1249-3p on TLR4/NF-κB axis activation is relieved, but not completely blocked in the presence of SMAD6 silencing (Fig. 6c, g, h and Supplementary Fig. S6c, g, h), suggesting that SMAD6 is essential to miR-1249-3p-mediated attenuated insulin resistance and inflammation, and other signaling pathways may exist in this process. This evidence concerns the gene SMAD6 and Insulin resistance.