Comparative analysis of hepatic miRNA levels in male marathon mice reveals a link between obesity and endurance exercise capacities.

Dummerstorf marathon mice (DUhTP) are characterized by increased accretion of peripheral body fat with fast mobilization in response to mild physical activity if running wheels were included in their home cages. The obese phenotype coincides with elevated hepatic lipogenesis if compared to unselected controls. We now asked, if microRNA (miRNA) species present in the liver may contribute to the obese phenotype of DUhTP mice and if miRNAs respond to mild physical activity in our mouse model. Total RNA was extracted from livers of sedentary or physically active marathon mice and controls and analyzed by array hybridization or real-time PCR using locked nucleic acid probes. Pathway analysis of altered miRNA concentrations identified fatty acid biosynthesis as the most important target for the effects of miRNAs in the liver. A miRNA signature consisting of miR-21, 27, 33, 122, and 143 was present at higher abundance (p < 0.01) in the liver of sedentary or active DUhTP mice indicating involvement of miRNAs with hepatic lipogenesis. Furthermore, in protein lysates from the liver of DUhTP mice, significantly reduced concentrations of total and phosphorylated AKT and lower levels of phosphorylated AMPK were found (p < 0.05). Our results indicate active involvement of miRNAs in the control of hepatic energy metabolism and discuss effects on signal transduction as a potentially direct effect of miR-143 in the liver of DUhTP mice.