ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
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- The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure.The journal of cardiovascular aging · 2023Article
- Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cardiac immune cell infiltration associates with abnormal lipid metabolism.Frontiers in cardiovascular medicine · 2022Article
- Modulation of de Novo Lipogenesis Improves Response to Enzalutamide Treatment in Prostate Cancer.Cancers · 2020Article
- Fish oil supplementation alleviates metabolic and anxiodepressive effects of diet-induced obesity and associated changes in brain lipid composition in mice.International journal of obesity (2005) · 2020Article
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- Follow-up of fatty acid β-oxidation disorders in expanded newborn screening era.European journal of pediatrics · 2019Article
- The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults.The Journal of nutrition · 2019Article
- Clinical, Biochemical, and Molecular Features in 37 Saudi Patients with Very Long Chain Acyl CoA Dehydrogenase Deficiency.JIMD reports · 2018Article
- The Complex QT/RR Relationship in Mice.Scientific reports · 2016Article
- Dampened Mesolimbic Dopamine Function and Signaling by Saturated but not Monounsaturated Dietary Lipids.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake.PloS one · 2015Article
- Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a high-fat diet and maintains endothelial function in mice.Journal of the American Heart Association · 2014Article
- Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance.American journal of physiology. Heart and circulatory physiology · 2014Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency frequently present cardiomyopathy and heartbeat disorders. However, the underlying factors, which may be of cardiac or extra cardiac origins, remain to be elucidated. In this study, we tested for metabolic and functional alterations in the heart from 3- and 7-mo-old VLCAD null mice and their littermate counterparts, using validated experimental paradigms, namely, 1) ex vivo perfusion in working mode, with concomitant evaluation of myocardial contractility and metabolic fluxes using (13)C-labeled substrates under various conditions; as well as 2) in vivo targeted lipidomics, gene expression analysis as well as electrocardiogram monitoring by telemetry in mice fed various diets. Unexpectedly, when perfused ex vivo, working VLCAD null mouse hearts maintained values similar to those of the controls for functional parameters and for the contribution of exogenous palmitate to β-oxidation (energy production), even at high palmitate concentration (1 mM) and increased energy demand (with 1 μM epinephrine) or after fasting. However, in vivo, these hearts displayed a prolonged rate-corrected QT (QTc) interval under all conditions examined, as well as the following lipid alterations: 1) age- and condition-dependent accumulation of triglycerides, and 2) 20% lower docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) in membrane phospholipids. The latter was independent of liver but affected by feeding a diet enriched in saturated fat (exacerbated) or fish oil (attenuated). Our finding of a longer QTc interval in VLCAD null mice appears to be most relevant given that such condition increases the risk of sudden cardiac death.
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