MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkt(s473) and pPI3K, and increased protein levels of pPTEN. G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkt(s473) and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin res stance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling.