title: Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes.
abstract: BACKGROUND
  Cardiac steatosis and apoptosis are key processes in diabetic cardiomyopathy, but the underlying mechanisms have not been elucidated, leading to a lack of effective therapy. The mineralocorticoid receptor blocker, eplerenone, has demonstrated anti-fibrotic actions in the diabetic heart. However, its effects on the fatty-acid accumulation and apoptotic responses have not been revealed.
  
  
  METHODS
  Non-hypertensive Zucker Diabetic Fatty (ZDF) rats received eplerenone (25 mg/kg) or vehicle. Zucker Lean (ZL) rats were used as control (n = 10, each group). After 16 weeks, cardiac structure and function was examined, and plasma and hearts were isolated for biochemical and histological approaches. Cultured cardiomyocytes were used for in vitro assays to determine the direct effects of eplerenone on high fatty acid and high glucose exposed cells.
  
  
  RESULTS
  In contrast to ZL, ZDF rats exhibited hyperglycemia, hyperlipidemia, insulin-resistance, cardiac steatosis and diastolic dysfunction. The ZDF myocardium also showed increased mitochondrial oxidation and apoptosis. Importantly, eplerenone mitigated these events without altering hyperglycemia. In cultured cardiomyocytes, high-concentrations of palmitate stimulated the fatty-acid uptake (in detriment of glucose assimilation), accumulation of lipid metabolites, mitochondrial dysfunction, and apoptosis. Interestingly, fatty-acid uptake, ceramides formation and apoptosis were also significantly ameliorated by eplerenone.
  
  
  CONCLUSIONS
  By blocking mineralocorticoid receptors, eplerenone may attenuate cardiac steatosis and apoptosis, and subsequent remodelling and diastolic dysfunction in obese/type-II diabetic rats.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ramírez
authors.forename: Mercedes
authors.initials: M
authors.lastname: Klett-Mingo
authors.forename: Sara
authors.initials: S
authors.lastname: Ares-Carrasco
authors.forename: Belén
authors.initials: B
authors.lastname: Picatoste
authors.forename: Alessia
authors.initials: A
authors.lastname: Ferrarini
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rupérez
authors.forename: Alicia
authors.initials: A
authors.lastname: Caro-Vadillo
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: José
authors.initials: J
authors.lastname: Tuñón
authors.affiliation: Cardiovascular Pathology laboratory, IIS-Fundación Jiménez Díaz, Autónoma University, Av, Reyes Católicos 2, Madrid 28040 Spain. olorenzo@fjd.es.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Lorenzo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003971:Diastole; D004195:Disease Models, Animal; D000077545:Eplerenone; D005227:Fatty Acids / Q000378:metabolism; D005355:Fibrosis; D005947:Glucose / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D018754:Ventricular Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016276:Ventricular Function / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D005227:Fatty Acids; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D005947:Glucose