Differential Expression of MicroRNAs in Mouse Liver under Aberrant Energy Metabolic Status

Despite years of effort, exact pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains obscure. To gain an insight into the regulatory roles of microRNAs (miRNAs) in aberrant energy metabolic status and pathogenesis of NAFLD, we analyzed the expression of miRNAs in livers of ob/ob mice, streptozotocin (STZ)-induced type 1 diabetic mice and normal C57BL/6 mice by miRNA microarray. Compared to normal C57BL/6 mice, ob/ob mice showed up-regulation of 8 miRNAs and down-regulation of 4 miRNAs in fatty livers. Up-regulation of miR-34a and down-regulation of miR-122 was found in livers of STZ-induced diabetic mice. These results demonstrate that distinct miRNAs are strongly dysregulated in NAFLD and hyperglycemia. Comparison between miRNA expressions in livers of ob/ob mice and STZ-administered mice further revealed up-regulation of 4 miRNAs and down-regulation of 2 miRNAs in livers of ob/ob mice, indicating that these miRNAs may represent a molecular signature of NAFLD. A distinctive miRNA expression pattern was identified in ob/ob mouse liver and hierarchical clustering of this pattern could clearly discriminate ob/ob mice from either normal C57BL/6 mice or STZ-administered mice. These findings suggest an important role of miRNAs in hepatic energy metabolism and implicate the participation of miRNAs in the pathophysiological processes of NAFLD. Keywords: disease state analysis In the present study, we analyzed the expression of miRNAs in livers of 10 ob/ob mice, 8 streptozotocin (STZ)-induced type 1 diabetic mice and 8 normal control C57BL/6 mice by miRNA microarray.