Increase of peroxisome proliferator-activated receptor δ (PPARδ) by digoxin to improve lipid metabolism in the heart of diabetic rats

Horm Metab Res. 2013 May;45(5):364-71. doi: 10.1055/s-0032-1330021. Epub 2012 Dec 7.

Abstract

Increase of peroxisome proliferator-activated receptor δ (PPARδ) expression by digoxin in the heart of diabetic rats has been documented. The present study investigated the mediation of PPARδ 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-PPARδ were employed to investigate the potential mechanisms. After a 20-day digoxin treatment, the PPARδ 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 PPARδ and fatty acid oxidation genes. But both actions of digoxin were blocked by BAPTA-AM to chelate calcium ions and by siRNA-PPARδ in cardiomyocytes. The obtained results show that increase of PPARδ by digoxin is related to regulation of fatty acid oxidation genes in cardiac cells mediated by calcium-triggered signals.

MeSH terms

  • Animals
  • Animals, Newborn
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Digoxin / pharmacology*
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Fatty Acids / metabolism
  • Gene Expression Regulation / drug effects
  • Hyperglycemia / complications
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / genetics
  • Myocardium / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidation-Reduction / drug effects
  • PPAR delta / metabolism*
  • RNA, Small Interfering / metabolism
  • Rats

Substances

  • Fatty Acids
  • PPAR delta
  • RNA, Small Interfering
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Digoxin