title: Fasting-induced myocardial lipid accumulation in long-chain acyl-CoA dehydrogenase knockout mice is accompanied by impaired left ventricular function.
abstract: BACKGROUND
  Lipotoxicity may be a key contributor to the pathogenesis of cardiac abnormalities in mitochondrial long-chain fatty acid β-oxidation (FAO) disorders. Few data are available on myocardial lipid levels and cardiac performance in FAO deficiencies. The purpose of this animal study is to assess fasting-induced changes in cardiac morphology, function, and triglyceride (TG) storage as a consequence of FAO deficiency in a noninvasive fashion.
  
  
  RESULTS
  MRI and proton magnetic resonance spectroscopy ((1)H-MRS) were applied in vivo in long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mice and wild-type (WT) mice (n=8 per genotype). Fasting was used to increase the heart's dependency on FAO for maintenance of energy homeostasis. In vivo data were complemented with ex vivo measurements of myocardial lipids. Left ventricular (LV) mass was higher in LCAD KO mice compared with WT mice (P<0.05), indicating LV myocardial hypertrophy. Myocardial TG content was higher in LCAD KO mice at baseline (P<0.001) and further increased in fasted LCAD KO mice (P<0.05). Concomitantly, LV ejection fraction (P<0.01) and diastolic filling rate (P<0.01) decreased after fasting, whereas these functional parameters did not change in fasted WT mice. Myocardial ceramide content was higher in fasted LCAD KO mice compared with fasted WT mice (P<0.05).
  
  
  CONCLUSIONS
  Using a noninvasive approach, this study reveals accumulation of myocardial TG in LCAD KO mice. Toxicity of accumulating lipid metabolites such as ceramides may be responsible for the fasting-induced impairment of cardiac function observed in the LCAD KO mouse.
authors: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors: Adrianus J
authors: AJ
authors: Bakermans
authors: Tom R
authors: TR
authors: Geraedts
authors: Michel
authors: M
authors: van Weeghel
authors: Simone
authors: S
authors: Denis
authors: Maria
authors: M
authors: João Ferraz
authors: Johannes M F G
authors: JM
authors: Aerts
authors: Jan
authors: J
authors: Aten
authors: Klaas
authors: K
authors: Nicolay
authors: Sander M
authors: SM
authors: Houten
authors: Jeanine J
authors: JJ
authors: Prompers
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005215:Fasting / Q000378:metabolism*; D005500:Follow-Up Studies; D050356:Lipid Metabolism; D019028:Magnetic Resonance Imaging, Cine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D014280:Triglycerides; D044942:Acyl-CoA Dehydrogenase, Long-Chain