Intensive research has identified that obesity often coexists with mitochondrial dysfunction, especially in the liver, featuring altered oxidative function, ultrastructure abnormalities, and increased oxidative stress, all of which are associated with deteriorated glucose metabolism in humans and mice. However, the severity of mitochondrial defects, the underlying molecular mechanisms, and the consequences for systemic glycemic control are not well established. Of note, some models of mitochondrial dysfunction fail to induce insulin resistance, and can even improve it. In addition, metformin, the most commonly prescribed therapeutic for T2D, inhibits hepatic mitochondrial respiration with improved hepatic and systemic glucose metabolism. These findings suggest a significant complexity between mitochondrial function and glycemic control. Dissecting the mechanisms by which altered mitochondrial function contributes to T2D, and how metformin remedies this disturbance, is of critical physiologic and clinical importance.
We have investigated the mitochondrial characteristics from a novel angle: by studying mitochondria-resident miRNA and their contribution to the mitochondrial complexity in glycemic control. We aim to better comprehend the roles of miRNA-mediated events in altered mitochondrial functions in the liver.