Gene expression profiling in hearts of diabetic mice uncovers a potential role of estrogen-related receptor γ in diabetic cardiomyopathy

Jaime Lasheras, Maria Vilà, Mònica Zamora, Efrén Riu, Rosario Pardo, Marcos Poncelas, Ildefonso Cases, Marisol Ruiz-Meana, Cristina Hernández, Juan E. Feliu, Rafael Simó, David García-Dorado, Josep A. Villena

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9 Citations (Scopus)

Abstract

© 2016 Elsevier Ireland Ltd Diabetic cardiomyopathy is characterized by an abnormal oxidative metabolism, but the underlying mechanisms remain to be defined. To uncover potential mechanisms involved in the pathophysiology of diabetic cardiomyopathy, we performed a gene expression profiling study in hearts of diabetic db/db mice. Diabetic hearts showed a gene expression pattern characterized by the up-regulation of genes involved in lipid oxidation, together with an abnormal expression of genes related to the cardiac contractile function. A screening for potential regulators of the genes differentially expressed in diabetic mice found that estrogen-related receptor γ (ERRγ) was increased in heart of db/db mice. Overexpression of ERRγ in cultured cardiomyocytes was sufficient to promote the expression of genes involved in lipid oxidation, increase palmitate oxidation and induce cardiomyocyte hypertrophy. Our findings strongly support a role for ERRγ in the metabolic alterations that underlie the development of diabetic cardiomyopathy.
Original languageEnglish
Pages (from-to)77-88
JournalMolecular and Cellular Endocrinology
Volume430
DOIs
Publication statusPublished - 15 Jul 2016

Keywords

  • Diabetes
  • Estrogen-related receptors
  • Fatty acid oxidation
  • Lipid metabolism
  • Orphan nuclear receptor
  • Transcriptional regulation of gene expression

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