title: Gene expression profiling in hearts of diabetic mice uncovers a potential role of estrogen-related receptor γ in diabetic cardiomyopathy.
abstract: 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.
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Lasheras
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vilà
authors.affiliation: Cell Biology Group, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; CIBER on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Zamora
authors.affiliation: Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Bellaterra, Spain; CIBER on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.
authors.forename: Efrén
authors.initials: E
authors.lastname: Riu
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pardo
authors.affiliation: Laboratory of Experimental Cardiology, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Poncelas
authors.affiliation: Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Cases
authors.affiliation: Laboratory of Experimental Cardiology, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Ruiz-Meana
authors.affiliation: CIBER on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Group of Diabetes and Metabolism, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Feliu
authors.affiliation: CIBER on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Group of Diabetes and Metabolism, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: Laboratory of Experimental Cardiology, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: García-Dorado
authors.affiliation: Laboratory of Metabolism and Obesity, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBER on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. Electronic address: josep.villena@vhir.org.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Villena
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: C490916:Esrrg protein, mouse; D047493:PPAR alpha; D011960:Receptors, Estrogen
keywords: Diabetes; Estrogen-related receptors; Fatty acid oxidation; Lipid metabolism; Orphan nuclear receptor; Transcriptional regulation of gene expression