Acadvl

Summary

Gene Symbol: Acadvl
Description: acyl-Coenzyme A dehydrogenase, very long chain
Alias: vlcad, very long-chain specific acyl-CoA dehydrogenase, mitochondrial, MVLCAD
Species: mouse
Products:     Acadvl

Top Publications

  1. Primassin S, ter Veld F, Mayatepek E, Spiekerkoetter U. Carnitine supplementation induces acylcarnitine production in tissues of very long-chain acyl-CoA dehydrogenase-deficient mice, without replenishing low free carnitine. Pediatr Res. 2008;63:632-7 pubmed publisher
    Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) results in accumulation of C14-C18 acylcarnitines and low free carnitine. Carnitine supplementation is still controversial...
  2. Primassin S, Tucci S, Herebian D, Seibt A, Hoffmann L, ter Veld F, et al. Pre-exercise medium-chain triglyceride application prevents acylcarnitine accumulation in skeletal muscle from very-long-chain acyl-CoA-dehydrogenase-deficient mice. J Inherit Metab Dis. 2010;33:237-46 pubmed publisher
    ..MCT-based diet compared with MCT administration only prior to exercise in very-long-chain acyl-CoA dehydrogenase (VLCAD) knockout (KO) mice...
  3. Kurtz D, Rinaldo P, Rhead W, Tian L, Millington D, Vockley J, et al. Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation. Proc Natl Acad Sci U S A. 1998;95:15592-7 pubmed
    ..Approximately 10% of adult LCAD -/- males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/- mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo. ..
  4. Aoyama T, Souri M, Ushikubo S, Kamijo T, Yamaguchi S, Kelley R, et al. Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients. J Clin Invest. 1995;95:2465-73 pubmed
    Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) was purified from human liver. The molecular masses of the native enzyme and the subunit were estimated to be 154 and 70 kD, respectively...
  5. Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, IJlst L, Vaz F, et al. Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice. Pediatr Res. 2005;57:760-4 pubmed
    Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD) is the most common long-chain fatty acid oxidation defect and presents with heterogeneous clinical manifestations...
  6. Goetzman E, Tian L, Wood P. Differential induction of genes in liver and brown adipose tissue regulated by peroxisome proliferator-activated receptor-alpha during fasting and cold exposure in acyl-CoA dehydrogenase-deficient mice. Mol Genet Metab. 2005;84:39-47 pubmed
    Mice deficient for either long-chain acyl-CoA dehydrogenase (LCAD-/-) or very-long-chain acyl-CoA dehydrogenase (VLCAD-/-) develop hepatic steatosis upon fasting, due to disrupted mitochondrial fatty acid oxidation...
  7. Cox K, Hamm D, Millington D, Matern D, Vockley J, Rinaldo P, et al. Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse. Hum Mol Genet. 2001;10:2069-77 pubmed
    Although many patients have been found to have very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, none have been documented with long-chain acyl-CoA dehydrogenase (LCAD) deficiency...
  8. Tucci S, Flogel U, Sturm M, Borsch E, Spiekerkoetter U. Disrupted fat distribution and composition due to medium-chain triglycerides in mice with a ?-oxidation defect. Am J Clin Nutr. 2011;94:439-49 pubmed publisher
  9. Skilling H, Coen P, Fairfull L, Ferrell R, Goodpaster B, Vockley J, et al. Brown adipose tissue function in short-chain acyl-CoA dehydrogenase deficient mice. Biochem Biophys Res Commun. 2010;400:318-22 pubmed publisher
    ..We speculate that other mechanisms such as shivering capacity, cardiac function, and reduced hepatic glycogen stores are involved. ..

More Information

Publications45

  1. Exil V, Roberts R, Sims H, McLaughlin J, Malkin R, Gardner C, et al. Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice. Circ Res. 2003;93:448-55 pubmed
    ..We generated very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)-deficient mice by homologous recombination to define the onset and molecular mechanism of myocardial disease...
  2. Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Exil V, Duran M, et al. Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress. Eur J Clin Invest. 2004;34:191-6 pubmed
    In humans with deficiency of the very long-chain acyl-CoA dehydrogenase (VLCAD), C14-C18 acylcarnitines accumulate...
  3. Gélinas R, Thompson Legault J, Bouchard B, Daneault C, Mansour A, Gillis M, et al. Prolonged QT interval and lipid alterations beyond ?-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts. Am J Physiol Heart Circ Physiol. 2011;301:H813-23 pubmed publisher
    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...
  4. Exil V, Gardner C, Rottman J, Sims H, Bartelds B, Khuchua Z, et al. Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase. Am J Physiol Heart Circ Physiol. 2006;290:H1289-97 pubmed
    Mitochondrial very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children...
  5. Spiekerkoetter U, Ruiter J, Tokunaga C, Wendel U, Mayatepek E, Wijburg F, et al. Evidence for impaired gluconeogenesis in very long-chain acyl-CoA dehydrogenase-deficient mice. Horm Metab Res. 2006;38:625-30 pubmed
    ..glucose production in FAO defects, we used the knockout mouse model of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency presenting with stress-induced hypoglycaemia...
  6. Primassin S, Tucci S, Spiekerkoetter U. Hepatic and muscular effects of different dietary fat content in VLCAD deficient mice. Mol Genet Metab. 2011;104:546-51 pubmed publisher
    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common long-chain fatty acid oxidation defect presenting with heterogeneous clinical phenotypes...
  7. Chegary M, Brinke H, Ruiter J, Wijburg F, Stoll M, Minkler P, et al. Mitochondrial long chain fatty acid beta-oxidation in man and mouse. Biochim Biophys Acta. 2009;1791:806-15 pubmed publisher
    ..of long chain acyl-CoA dehydrogenase knockout (LCAD(-/-)), very long chain acyl-CoA dehydrogenase knockout (VLCAD(-/-)) and wild type mice with fibroblasts of VLCAD-deficient patients and human controls...
  8. Aoyama T, Uchida Y, Kelley R, Marble M, Hofman K, Tonsgard J, et al. A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase. Biochem Biophys Res Commun. 1993;191:1369-72 pubmed
    ..presence and absence of antibodies against medium-chain, long-chain, and very-long-chain acyl-CoA dehydrogenases (VLCAD)...
  9. Tucci S, Primassin S, Spiekerkoetter U. Fasting-induced oxidative stress in very long chain acyl-CoA dehydrogenase-deficient mice. FEBS J. 2010;277:4699-708 pubmed publisher
    ..Here, we investigated the effects of prolonged fasting and an MCT diet on liver function. Wild-type (WT) and VLCAD knockout mice were fed with either a regular long-chain triglyceride diet or an MCT diet for 5 weeks...
  10. Tucci S, Primassin S, ter Veld F, Spiekerkoetter U. Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice. Mol Genet Metab. 2010;101:40-7 pubmed publisher
    ..Wild-type (WT) and VLCAD-knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5weeks, (2) an MCT diet over 5 weeks ..
  11. Andresen B, Corydon T, Wilsbech M, Bross P, Schroeder L, Hindkjaer T, et al. Characterization of mouse Clpp protease cDNA, gene, and protein. Mamm Genome. 2000;11:275-80 pubmed
  12. Lai L, Leone T, Zechner C, Schaeffer P, Kelly S, Flanagan D, et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008;22:1948-61 pubmed publisher
    ..We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. ..
  13. Tucci S, Flogel U, Hermann S, Sturm M, Schäfers M, Spiekerkoetter U. Development and pathomechanisms of cardiomyopathy in very long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice. Biochim Biophys Acta. 2014;1842:677-85 pubmed publisher
    ..We here characterize cardiac function of VLCAD-deficient (VLCAD(-/-)) mice over one year...
  14. Tucci S, Behringer S, Spiekerkoetter U. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids. FEBS J. 2015;282:4242-53 pubmed publisher
    ..medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD)...
  15. Cox K, Liu J, Tian L, Barnes S, Yang Q, Wood P. Cardiac hypertrophy in mice with long-chain acyl-CoA dehydrogenase or very long-chain acyl-CoA dehydrogenase deficiency. Lab Invest. 2009;89:1348-54 pubmed publisher
    ..Mice with either very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD-/-) or long-chain acyl-coenzyme A dehydrogenase deficiency (LCAD-/-) develop cardiac hypertrophy...
  16. Schuler A, Gower B, Matern D, Rinaldo P, Vockley J, Wood P. Synergistic heterozygosity in mice with inherited enzyme deficiencies of mitochondrial fatty acid beta-oxidation. Mol Genet Metab. 2005;85:7-11 pubmed
    ..acyl CoA dehydrogenase, long-chain acyl CoA dehydrogenase, and short-chain acyl CoA dehydrogenase genes (VLCAD+/-//LCAD+/-//SCAD+/-); double heterozygosity for mutations in VLCAD and LCAD genes (VLCAD+/-//LCAD+/-); double ..
  17. Keeler A, Conlon T, Walter G, Zeng H, Shaffer S, Dungtao F, et al. Long-term correction of very long-chain acyl-coA dehydrogenase deficiency in mice using AAV9 gene therapy. Mol Ther. 2012;20:1131-8 pubmed publisher
    Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation...
  18. Tucci S, Pearson S, Herebian D, Spiekerkoetter U. Long-term dietary effects on substrate selection and muscle fiber type in very-long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice. Biochim Biophys Acta. 2013;1832:509-16 pubmed publisher
    ..fat restriction and increased carbohydrate intake are part of treatment in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency, the most common defect of long-chain fatty acid oxidation...
  19. Diekman E, van Weeghel M, Wanders R, Visser G, Houten S. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models. FASEB J. 2014;28:2891-900 pubmed publisher
    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid ?-oxidation (FAO)...
  20. Tucci S, Mingirulli N, Wehbe Z, Dumit V, Kirschner J, Spiekerkoetter U. Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice. FEBS Lett. 2018;592:219-232 pubmed publisher
    The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD-/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by ..
  21. Berger J, Truppe C, Neumann H, Forss Petter S. cDNA cloning and mRNA distribution of a mouse very long-chain acyl-CoA synthetase. FEBS Lett. 1998;425:305-9 pubmed
  22. Orii K, Aoyama T, Saito Ohara F, Ikeuchi T, Orii T, Kondo N, et al. Molecular characterization of the mouse very-long-chain acyl-CoA dehydrogenase gene. Mamm Genome. 1997;8:516-8 pubmed
  23. Tucci S, Herebian D, Sturm M, Seibt A, Spiekerkoetter U. Tissue-specific strategies of the very-long chain acyl-CoA dehydrogenase-deficient (VLCAD-/-) mouse to compensate a defective fatty acid ?-oxidation. PLoS ONE. 2012;7:e45429 pubmed
    Very long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency is the most common long-chain fatty acid oxidation disorder presenting with heterogeneous phenotypes...
  24. Schiff M, Haberberger B, Xia C, Mohsen A, Goetzman E, Wang Y, et al. Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency. Hum Mol Genet. 2015;24:3238-47 pubmed publisher
    ..Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunctions. ..
  25. Riggs C, Michaelides M, Parpa K, Smith Blair N. The effects of aerobic interval training on the left ventricular morphology and function of VLCAD-deficient mice. Eur J Appl Physiol. 2010;110:915-23 pubmed publisher
    This study examined the effect of aerobic interval training on cardiac adaptations in VLCAD-deficient mice and determined the effects of the deficiency on the morphology and function of the left ventricle among 53 knockout homozygous ..
  26. Zhang D, Christianson J, Liu Z, Tian L, Choi C, Neschen S, et al. Resistance to high-fat diet-induced obesity and insulin resistance in mice with very long-chain acyl-CoA dehydrogenase deficiency. Cell Metab. 2010;11:402-11 pubmed publisher
    ..an inherited deficiency of the mitochondrial fatty acid oxidation enzyme, very long-chain acyl-CoA dehydrogenase (VLCAD), were protected from high-fat diet-induced obesity and liver and muscle insulin resistance...
  27. Tucci S, Floegel U, Beermann F, Behringer S, Spiekerkoetter U. Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse. J Lipid Res. 2017;58:196-207 pubmed publisher
    ..of a 1-year triheptanoin-based diet on the clinical phenotype of very long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD-/-) mice. The cardiac function was assessed in VLCAD-/- mice by in vivo MRI...
  28. Tucci S, Flögel U, Spiekerkoetter U. Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT). Biochim Biophys Acta. 2015;1852:1442-50 pubmed publisher
    ..We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet...
  29. ter Veld F, Primassin S, Hoffmann L, Mayatepek E, Spiekerkoetter U. Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice. J Lipid Res. 2009;50:1556-62 pubmed publisher
    ..To test whether this increase in long-chain acylcarnitines in very long-chain acyl-CoA dehydrogenase (VLCAD(-/-)) knock-out mice correlates with acyl-CoA content, we subjected wild-type (WT) and VLCAD(-/-) mice to forced ..
  30. Xiong D, He H, James J, Tokunaga C, Powers C, Huang Y, et al. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance. Am J Physiol Heart Circ Physiol. 2014;306:H326-38 pubmed publisher
    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial ?-oxidation...
  31. Cardoso A, Kakimoto P, Kowaltowski A. Diet-sensitive sources of reactive oxygen species in liver mitochondria: role of very long chain acyl-CoA dehydrogenases. PLoS ONE. 2013;8:e77088 pubmed publisher
    ..were found to be more highly expressed in HFD livers, although only the very long chain acyl-CoA dehydrogenase (VLCAD) was more functionally active...
  32. Zhang Y, Bharathi S, Rardin M, Uppala R, Verdin E, Gibson B, et al. SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain acyl-CoA dehydrogenase. PLoS ONE. 2015;10:e0122297 pubmed publisher
    ..Here, we demonstrate that SIRT3 and SIRT5 both target human very long-chain acyl-CoA dehydrogenase (VLCAD), a key fatty acid oxidation enzyme...
  33. Orii K, Saito Ohara F, Ikeuchi T, Orii T, Kondo N, Aoyama T, et al. Assignment of the gene for very-long-chain acyl-CoA dehydrogenase (Acadvl) to mouse chromosome band 11B2-B5 by in situ hybridization. Cytogenet Cell Genet. 1997;78:25-6 pubmed
  34. Exil V, Silva Avila D, Benedetto A, Exil E, Adams M, Au C, et al. Stressed-induced TMEM135 protein is part of a conserved genetic network involved in fat storage and longevity regulation in Caenorhabditis elegans. PLoS ONE. 2010;5:e14228 pubmed publisher
    ..elegans). We have previously documented a mouse model of mitochondrial very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency...
  35. Luo B, Zou T, Lu N, Chai F, Ye X, Wang Y, et al. Role of suppressor of cytokine signaling 3 in lipid metabolism: analysis based on a phage-display human liver cDNA library. Biochem Biophys Res Commun. 2011;416:39-44 pubmed publisher
    ..to the sequence of amino acids 644-655 of C-terminal extra-polypeptide of very-long-chain acyl-CoA dehydrogenase (VLCAD), which is 1 of 4 flavoproteins that catalyzing the initial step of the mitochondrial fatty acid ?-oxidation, ..
  36. Wolfrum C, Asilmaz E, Luca E, Friedman J, Stoffel M. Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature. 2004;432:1027-32 pubmed
    ..Pharmacological intervention to inhibit phosphorylation of Foxa2 may be an effective treatment for type 2 diabetes. ..