Increase of peroxisome proliferator-activated receptor delta (PPAR delta) expression by digoxin in the heart of diabetic rats has been documented. The present study investigated the mediation of PPAR delta in lipid metabolism improved by digoxin in the heart of diabetic rats and in the hyperglycemia-treated cardiomyocytes using the primary cultured cardiomyocytes from neonatal rat. The lipid deposition within the heart section was assessed in diabetic rats by oil red O staining. The fatty acid oxidation genes in cardiomyocytes were also examined. Inhibitor of calcium ions and siRNA-PPAR delta were employed to investigate the potential mechanisms. After a 20-day digoxin treatment, the PPAR delta expression was elevated in hearts of diabetic rats while the cardiac lipid deposition was reduced. In neonatal cardiomyocytes, digoxin also caused an increase in expressions of PPAR delta and fatty acid oxidation genes. But both actions of digoxin were blocked by BAPTA-AM to chelate calcium ions and by siRNA-PPAR delta in cardiomyocytes. The obtained results show that increase of PPAR delta by digoxin is related to regulation of fatty acid oxidation genes in cardiac cells mediated by calcium-triggered signals.
Hormone And Metabolic Research, v.45 n.5, pp.364-371