Fasting-induced myocardial lipid accumulation in long-chain acyl-coa dehydrogenase knockout mice is accompanied by impaired left ventricular function

Adrianus J. Bakermans, Tom R. Geraedts, Michel Van Weeghel, Simone Denis, Maria João Ferraz, Johannes M.F.G. Aerts, Jan Aten, Klaas Nicolay, Sander M. Houten, Jeanine J. Prompers

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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. Methods and Results-MRI and proton magnetic resonance spectroscopy (1H-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).

Original languageEnglish
Pages (from-to)558-565
Number of pages8
JournalCirculation: Cardiovascular Imaging
Volume4
Issue number5
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • Hypertrophy
  • Lipids
  • MRI
  • Metabolism
  • Spectroscopy

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