MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα

BackgroundMetabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood.ResultsDb/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were employed in the current study. Microarray data analysis revealed that PGC-1 may play an important role in DCM. Downregulation of PGC-1 relieved palmitate induced cardiac metabolism shift to fatty acids use and relevant lipotoxicity in vitro. Bioinformatics coupled with biochemical validation was used to confirm that PGC-1 was one of the direct targets of miR-30c. Remarkably, overexpression of miR-30c by rAAV system improved glucose utilization, reduced excessive reactive oxygen species production and myocardial lipid accumulation, and subsequently attenuated cardiomyocyte apoptosis and cardiac dysfunction in db/db mice. Similar effects were also observed in cultured cells. More importantly, miR-30c overexpression as well as PGC-1 knockdown reduced the transcriptional activity of PPAR, and the effects of miR-30c on PPAR was almost abated by PGC-1 knockdown.ConclusionsOur data demonstrated a protective role of miR-30c in cardiac metabolism in diabetes via targeting PGC-1, and suggested that modulation of PGC-1 by miR-30c may provide a therapeutic approach for DCM.