title: Chronic ethanol consumption increases cardiomyocyte fatty acid uptake and decreases ventricular contractile function in C57BL/6J mice.
abstract: Alcohol, a major cause of human cardiomyopathy, decreases cardiac contractility in both animals and man. However, key features of alcohol-related human heart disease are not consistently reproduced in animal models. Accordingly, we studied cardiac histology, contractile function, cardiomyocyte long chain fatty acid (LCFA) uptake, and gene expression in male C57BL/6J mice consuming 0, 10, 14, or 18% ethanol in drinking water for 3months. At sacrifice, all EtOH groups had mildly decreased body and increased heart weights, dose-dependent increases in cardiac triglycerides and a marked increase in cardiac fatty acid ethyl esters. [(3)H]-oleic acid uptake kinetics demonstrated increased facilitated cardiomyocyte LCFA uptake, associated with increased expression of genes encoding the LCFA transporters CD36 and Slc27a1 (FATP1) in EtOH-fed animals. Although SCD-1 expression was increased, lipidomic analysis did not indicate significantly increased de novo LCFA synthesis. By echocardiography, ejection fraction (EF) and the related fractional shortening (FS) of left ventricular diameter during systole were reduced and negatively correlated with cardiac triglycerides. Expression of myocardial PGC-1α and multiple downstream target genes in the oxidative phosphorylation pathway, including several in the electron transport and ATP synthase complexes of the inner mitochondrial membrane, were down-regulated. Cardiac ATP was correspondingly reduced. The data suggest that decreased expression of PGC-1α and its target genes result in decreased cardiac ATP levels, which may explain the decrease in myocardial contractile function caused by chronic EtOH intake. This model recapitulates important features of human alcoholic cardiomyopathy and illustrates a potentially important pathophysiologic link between cardiac lipid metabolism and function.
authors: The Department of Medicine, Division of Digestive & Liver Disease, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors: Chunguang
authors: C
authors: Hu
authors: Fengxia
authors: F
authors: Ge
authors: Eiichi
authors: E
authors: Hyodo
authors: Kotaro
authors: K
authors: Arai
authors: Shinichi
authors: S
authors: Iwata
authors: Harrison
authors: H
authors: Lobdell
authors: José L
authors: JL
authors: Walewski
authors: Shengli
authors: S
authors: Zhou
authors: Robin D
authors: RD
authors: Clugston
authors: Hongfeng
authors: H
authors: Jiang
authors: Cynthia P
authors: CP
authors: Zizola
authors: Kalyani G
authors: KG
authors: Bharadwaj
authors: William S
authors: WS
authors: Blaner
authors: Shunichi
authors: S
authors: Homma
authors: P Christian
authors: PC
authors: Schulze
authors: Ira J
authors: IJ
authors: Goldberg
authors: Paul D
authors: PD
authors: Berk
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004452:Echocardiography; D000431:Ethanol / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005227:Fatty Acids; D000431:Ethanol