Acadl

Summary

Gene Symbol: Acadl
Description: acyl-Coenzyme A dehydrogenase, long-chain
Alias: AA960361, AU018452, C79855, LCAD, long-chain specific acyl-CoA dehydrogenase, mitochondrial, acetyl-Coenzyme A dehydrogenase, long-chain
Species: mouse
Products:     Acadl

Top Publications

  1. 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...
  2. Hirschey M, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard D, et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010;464:121-5 pubmed publisher
    ..Mass spectrometry of mitochondrial proteins shows that long-chain acyl coenzyme A dehydrogenase (LCAD) is hyperacetylated at lysine 42 in the absence of SIRT3...
  3. Irie J, Reck B, Wu Y, Wicker L, Howlett S, Rainbow D, et al. Genome-wide microarray expression analysis of CD4+ T Cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes. J Immunol. 2008;180:1071-9 pubmed
    ..These results validate the approach of using congenic mice together with genome-wide analysis of tissue-specific gene expression to identify novel candidate genes in T1D...
  4. 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
    ..Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO)...
  5. 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
    ..acyl-CoA dehydrogenase (VLCAD) deficiency, none have been documented with long-chain acyl-CoA dehydrogenase (LCAD) deficiency...
  6. 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
    ..biochemical and molecular methods, we compared fibroblasts of long chain acyl-CoA dehydrogenase knockout (LCAD(-/-)), very long chain acyl-CoA dehydrogenase knockout (VLCAD(-/-)) and wild type mice with fibroblasts of VLCAD-..
  7. Zhang D, Liu Z, Choi C, Tian L, Kibbey R, Dong J, et al. Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance. Proc Natl Acad Sci U S A. 2007;104:17075-80 pubmed
    ..can cause insulin resistance, we studied mice with a deficiency of long-chain acyl-CoA dehydrogenase (LCAD), a key enzyme in mitochondrial fatty acid oxidation...
  8. 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
  9. Hall C, Heijkenskjöld L, Bartfai T, Ernster L, Kamin H. Acyl coenzyme A dehydrogenases and electron-transferring flavoprotein from beef hart mitochondria. Arch Biochem Biophys. 1976;177:402-14 pubmed

More Information

Publications40

  1. Hinsdale M, Farmer S, Johnson K, Davisson M, Hamm D, Tolwani R, et al. RNA expression and chromosomal location of the mouse long-chain acyl-CoA dehydrogenase gene. Genomics. 1995;28:163-70 pubmed
    The cDNA for mouse long-chain acyl-CoA dehydrogenase (Acadl, gene symbol; LCAD, enzyme) was cloned and characterized. The cDNA was obtained by library screening and reverse transcription-polymerase chain reaction (RT-PCR)...
  2. 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. ..
  3. Kurtz D, Tolwani R, Wood P. Structural characterization of the mouse long-chain acyl-CoA dehydrogenase gene and 5' regulatory region. Mamm Genome. 1998;9:361-5 pubmed
    ..role of LCAD in this pathway, we have cloned and characterized the entire mouse (Mus musculus) gene encoding LCAD (Acadl). Acadl is a single-copy, nuclear encoded gene approximately 35 kb in size...
  4. Bjorkegren J, Veniant M, Kim S, Withycombe S, Wood P, Hellerstein M, et al. Lipoprotein secretion and triglyceride stores in the heart. J Biol Chem. 2001;276:38511-7 pubmed
    ..Thus, heart lipoprotein secretion helps regulate cardiac triglyceride stores and may protect the heart from the detrimental effects of surplus lipids. ..
  5. Uddin M, Joe Y, Zheng M, Kim S, Lee H, Kwon T, et al. Inhibitory Effects of Chung Hun Wha Dam Tang (CHWDT) on High-Fat Diet-Induced Obesity via AMP-Activated Protein Kinase Activation. Evid Based Complement Alternat Med. 2012;2012:652473 pubmed publisher
    ..Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1?, G6Pase, PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro...
  6. Pougovkina O, te Brinke H, Ofman R, van Cruchten A, Kulik W, Wanders R, et al. Mitochondrial protein acetylation is driven by acetyl-CoA from fatty acid oxidation. Hum Mol Genet. 2014;23:3513-22 pubmed publisher
  7. Otsubo C, Bharathi S, Uppala R, Ilkayeva O, Wang D, McHugh K, et al. Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant. J Biol Chem. 2015;290:23897-904 pubmed publisher
    ..observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD)...
  8. Ruiz Lozano P, Smith S, Perkins G, Kubalak S, Boss G, Sucov H, et al. Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos. Development. 1998;125:533-44 pubmed
    ..We propose a model whereby defects in intermediary metabolism may be a causative factor of the RXRalpha-/- phenotype and resembles an embryonic form of dilated cardiomyopathy. ..
  9. Almodovar A, Luther R, Stonebrook C, Wood P. Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice. Mol Genet Metab. 2013;110:396-400 pubmed publisher
    ..four representative C57BL/6 (B6) congenic mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl), B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3), and D) a replacement of mouse ..
  10. 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
    ..The data obtained from our experiments suggest that TMEM135 is part of a regulatory circuit that plays a critical role in the survival of VLCAD-deficient mice and perhaps in other mitochondrial genetic defects of fat metabolism as well. ..
  11. Berger P, Wood P. Disrupted blastocoele formation reveals a critical developmental role for long-chain acyl-CoA dehydrogenase. Mol Genet Metab. 2004;82:266-72 pubmed
    Long-chain acyl-CoA dehydrogenase (LCAD) deficiency has not been found in human patients. There has been an LCAD deficient (LCAD-/-) mouse model developed via gene targeting strategies that has gestational loss as a part of its phenotype...
  12. Goetzman E, Alcorn J, Bharathi S, Uppala R, McHugh K, Kosmider B, et al. Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction. J Biol Chem. 2014;289:10668-79 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver...
  13. Martin J, Balmer M, Rajendran S, Maurhofer O, Dufour J, St Pierre M. Nutritional stress exacerbates hepatic steatosis induced by deletion of the histidine nucleotide-binding (Hint2) mitochondrial protein. Am J Physiol Gastrointest Liver Physiol. 2016;310:G497-509 pubmed publisher
    ..The absence of Hint2 deregulates the posttranslational modification of several mitochondrial proteins, which impedes the adaptation to episodes of nutritional stress. ..
  14. Indo Y, Yang Feng T, Glassberg R, Tanaka K. Molecular cloning and nucleotide sequence of cDNAs encoding human long-chain acyl-CoA dehydrogenase and assignment of the location of its gene (ACADL) to chromosome 2. Genomics. 1992;12:626 pubmed
  15. Yubero P, Hondares E, Carmona M, Rossell M, Gonzalez F, Iglesias R, et al. The developmental regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression in the liver is partially dissociated from the control of gluconeogenesis and lipid catabolism. Endocrinology. 2004;145:4268-77 pubmed
  16. Schuler A, Gower B, Matern D, Rinaldo P, Wood P. Influence of dietary fatty acid chain-length on metabolic tolerance in mouse models of inherited defects in mitochondrial fatty acid beta-oxidation. Mol Genet Metab. 2004;83:322-9 pubmed
    ..has on a patient's ability to compensate during a metabolic challenge, we fed long-chain acyl CoA dehydrogenase (LCAD) deficient and short-chain acyl CoA dehydrogenase (SCAD) deficient mice a diet rich in medium-chain triglycerides (..
  17. Zhang Y, Bharathi S, Rardin M, Lu J, Maringer K, Sims Lucas S, et al. Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain. J Biol Chem. 2017;292:10239-10249 pubmed publisher
    ..Our findings suggest that SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin to promote respiratory chain function. ..
  18. Houten S, Herrema H, te Brinke H, Denis S, Ruiter J, van Dijk T, et al. Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects. Hum Mol Genet. 2013;22:5249-61 pubmed publisher
    ..this study, we have systematically addressed the fasting response in long-chain acyl-CoA dehydrogenase-deficient (LCAD KO) mice...
  19. Luther R, Almodovar A, Fullerton R, Wood P. Acadl-SNP based genotyping assay for long-chain acyl-CoA dehydrogenase deficient mice. Mol Genet Metab. 2012;106:62-7 pubmed publisher
    The long-chain acyl-CoA dehydrogenase (LCAD) (Acadl=gene; LCAD=protein) deficient mouse model has been important in evaluating the role of mitochondrial fatty acid oxidation of long-chain fatty acids in metabolic disorders...
  20. Bakermans A, Dodd M, Nicolay K, Prompers J, Tyler D, Houten S. Myocardial energy shortage and unmet anaplerotic needs in the fasted long-chain acyl-CoA dehydrogenase knockout mouse. Cardiovasc Res. 2013;100:441-9 pubmed publisher
    ..dehydrogenase (PDH) activity in fed and fasted wild-type (WT) mice and long-chain acyl-CoA dehydrogenase knockout (LCAD KO) mice. PDH activity decreased after fasting in both genotypes, but was 2...
  21. Hamilton Williams E, Cheung J, Rainbow D, Hunter K, Wicker L, Sherman L. Cellular mechanisms of restored β-cell tolerance mediated by protective alleles of Idd3 and Idd5. Diabetes. 2012;61:166-74 pubmed publisher
    ..alleles encoding IL-2, Idd3 candidate gene, CTLA-4, NRAMP1, and acetyl-coenzyme A dehydrogenase, long-chain (ACADL) (candidate genes for the Idd5.1, Idd5.2, and Idd5.3 subregions) provide nearly complete diabetes protection...
  22. 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 ..
  23. Chen T, Liu J, Li N, Wang S, Liu H, Li J, et al. Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD. PLoS ONE. 2015;10:e0118909 pubmed publisher
    ..hearts and that this change was accompanied by a higher acetylation level of long-chain acyl CoA dehydrogenase (LCAD), which is a key enzyme participating in fatty acid oxidation...
  24. 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
    ..acyl-coenzyme A dehydrogenase deficiency (VLCAD-/-) or long-chain acyl-coenzyme A dehydrogenase deficiency (LCAD-/-) develop cardiac hypertrophy...
  25. 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
    ..The expression of the mitochondrial long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was quantified at mRNA and protein level in heart, liver and ..
  26. Bharathi S, Zhang Y, Mohsen A, Uppala R, Balasubramani M, Schreiber E, et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J Biol Chem. 2013;288:33837-47 pubmed publisher
    Long-chain acyl-CoA dehydrogenase (LCAD) is a key mitochondrial fatty acid oxidation enzyme...
  27. 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
    ..phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (..
  28. 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. ..
  29. Bakermans A, Geraedts T, van Weeghel M, Denis S, Joao Ferraz M, Aerts J, et al. Fasting-induced myocardial lipid accumulation in long-chain acyl-CoA dehydrogenase knockout mice is accompanied by impaired left ventricular function. Circ Cardiovasc Imaging. 2011;4:558-65 pubmed publisher
    ..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)...
  30. Guerra C, Koza R, Walsh K, Kurtz D, Wood P, Kozak L. Abnormal nonshivering thermogenesis in mice with inherited defects of fatty acid oxidation. J Clin Invest. 1998;102:1724-31 pubmed
    ..came from our finding that mice carrying the targeted inactivation of the long chain acyl CoA dehydrogenase gene (Acadl) are also sensitive to the cold...
  31. Bakermans A, van Weeghel M, Denis S, Nicolay K, Prompers J, Houten S. Carnitine supplementation attenuates myocardial lipid accumulation in long-chain acyl-CoA dehydrogenase knockout mice. J Inherit Metab Dis. 2013;36:973-81 pubmed publisher
    ..carnitine supplementation in an animal model of long-chain FAO deficiency, the long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mouse...