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.