title: Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse.
abstract: A rather new approach in the treatment of long-chain fatty acid oxidation disorders is represented by triheptanoin, a triglyceride with three medium-odd-chain heptanoic acids (C7), due to its anaplerotic potential. We here investigate the effects 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. Metabolic adaptations were identified by the expression of genes regulating energy metabolism and anaplerotic processes using real-time PCR, and the results were correlated with the measurement of the glycolytic enzymes pyruvate dehydrogenase and pyruvate kinase. Finally, the intrahepatic lipid accumulation and oxidative stress in response to the long-term triheptanoin diet were assessed. Triheptanoin was not able to prevent the development of systolic dysfunction in VLCAD-/-mice despite an upregulation of cardiac glucose oxidation. Strikingly, the anaplerotic effects of triheptanoin were restricted to the liver. Despite this, the hepatic lipic content was increased upon triheptanoin supplementation. Our data demonstrate that the concept of anaplerosis does not apply to all tissues equally.
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany sara.tucci@uniklinik-freiburg.de.
authors.forename: Sara
authors.initials: S
authors.lastname: Tucci
authors.affiliation: Department of Molecular Cardiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Floegel
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Beermann
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Sidney
authors.initials: S
authors.lastname: Behringer
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics*; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D006538:Heptanoic Acids / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D014280:Triglycerides / Q000008:administration & dosage*
chemical_list: D005227:Fatty Acids; D006538:Heptanoic Acids; D014280:Triglycerides; C531010:triheptanoin; D044942:Acyl-CoA Dehydrogenase, Long-Chain
keywords: VLCAD deficiency; anaplerosis; cardiac function