Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in male models of diabetes and obesity

The miR-379/miR-410 cluster, belonging to the Dlk1-Dio3 locus, is the largest cluster of miRNAs in mammals. Most of its components are predicted to regulate insulin signaling, and we found consistent upregulation of the cluster in the livers of obese subjects as well as of different experimental models of insulin resistance. We have engineered a tool, a TuD, able to target two microRNAs from the cluster in a liver-specific manner. As a result, the cluster is repressed, which activates insulin signaling in the liver and leads to enhanced hepatic insulin sensitivity and reduced hepatic glucose output. This dataset includes transcriptomics data from liver tissue of young male mice carrying hepatic-specific expression of a TuD inhibitor able to repress the miR-379/miR-410 cluster (n=6) or a negative control sequence (n=5).