MicroRNA-802 increases hepatic oxidative stress and induces insulin resistance in high-fat fed mice

The expression of microRNA-802 (miR-802) is known to be associated with insulin resistance (IR); however, the mechanism remains unclear. The present study investigated how miR-802 contributes to the development of IR using C57BL/6J mice fed a high-fat diet (HFD) to establish a model of IR. Adeno-associated virus overexpressing miR-802 was administered to the mice via tail vein injection. The effects of miR-802 on reactive oxygen species (ROS), lipid peroxidation (LPO) and the activities of multiple ROS-related enzymes were investigated. Western blot analysis was used to estimate the protein levels of extracellular signal regulated kinase (ERK), p38mitogen-activated protein kinases (p38MAPK), c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS-1) and protein kinase B (AKT1). The results demonstrated that the levels of ROS and LPO production were increased in the livers of the miR-802-treated group compared with the control group. The activities of the ROS-related enzymes were reduced. Furthermore, the expression of phosphorylated (phosphor)-p38MAPK and phosphor-JNK were upregulated in the miR-802 overexpression group, whereas there was no difference in the expression levels of phosphor-ERK. The expression levels of phosphor-AKT1 were reduced in the miR-802-treated group and these effects were reversed by miR-802 knockdown. In conclusion, the results demonstrate that miR-802 may cause IR by activating the JNK and p38MAPK pathways to increase hepatic oxidative stress.