title: Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice.
abstract: Obesity is a significant risk factor for the development of cardiovascular disease. Inhibiting fatty acid oxidation has emerged as a novel approach for the treatment of ischemic heart disease. Our aim was to determine whether pharmacologic inhibition of 3-ketoacyl-coenzyme A thiolase (3-KAT), which catalyzes the final step of fatty acid oxidation, could improve obesity-induced cardiomyopathy. A 3-week treatment with the 3-KAT inhibitor trimetazidine prevented obesity-induced reduction in both systolic and diastolic function. Therefore, targeting cardiac fatty acid oxidation may be a novel therapeutic approach to alleviate the growing burden of obesity-related cardiomyopathy.
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: John R
authors: JR
authors: Ussher
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Natasha
authors: N
authors: Fillmore
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Wendy
authors: W
authors: Keung
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Jun
authors: J
authors: Mori
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Donna L
authors: DL
authors: Beker
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Cory S
authors: CS
authors: Wagg
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors: Jagdip S
authors: JS
authors: Jaswal
authors: Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: gary.lopaschuk@ualberta.ca.
authors: Gary D
authors: GD
authors: Lopaschuk
mesh_terms: D000102:Acetyl-CoA C-Acyltransferase / Q000037:antagonists & inhibitors; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D004452:Echocardiography; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D014292:Trimetazidine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010168:Palmitates; D014665:Vasodilator Agents; D000102:Acetyl-CoA C-Acyltransferase; D014292:Trimetazidine