title: Effect of carnitine deprivation on carnitine homeostasis and energy metabolism in mice with systemic carnitine deficiency.
abstract: OBJECTIVE
  Juvenile visceral steatosis (jvs-/-) mice lack the activity of the carnitine transporter OCTN2 and are dependent on carnitine substitution. The effects of carnitine deprivation on carnitine homeostasis and energy metabolism are not known in jvs-/- mice.
  
  
  METHODS
  jvs-/- mice were studied 3, 6 and 10 days after carnitine deprivation, and compared to jvs-/- mice substituted with carnitine, wild-type (jvs+/+) and jvs+/- mice. Carnitine concentrations were assessed radioenzymatically.
  
  
  RESULTS
  Compared to wild-type mice, carnitine-treated jvs-/- mice had decreased plasma beta-hydroxybutyrate levels and showed hepatic fat accumulation. The carnitine levels in plasma, liver and skeletal muscle were decreased by 58, 16 and 17%, respectively. After ten days of carnitine deprivation, the plasma carnitine concentration had fallen by 87% (to 2.3 mumol/l) and the tissue carnitine levels by approximately 50% compared to carnitine-treated jvs-/- mice. Carnitine deprivation was associated with a further drop in plasma beta-hydroxybutyrate and increased hepatic fat. Skeletal muscle glycogen stores decreased and lactate levels increased with carnitine deprivation, whereas tissue ATP levels were maintained.
  
  
  CONCLUSIONS
  In jvs-/- mice, tissue carnitine stores are more resistant than carnitine plasma concentrations to carnitine deprivation. Metabolic changes (liver steatosis and loss of muscle glycogen stores) appear also early after carnitine deprivation.
authors.affiliation: Division of Clinical Pharmacology and Toxicology and Department of Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Andrea Caroline
authors.initials: AC
authors.lastname: Knapp
authors.forename: Liliane
authors.initials: L
authors.lastname: Todesco
authors.forename: Michael
authors.initials: M
authors.lastname: Torok
authors.forename: Konstantin
authors.initials: K
authors.lastname: Beier
authors.forename: Stephan
authors.initials: S
authors.lastname: Krähenbühl
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001835:Body Weight; D002331:Carnitine / Q000008:administration & dosage / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use; D004734:Energy Metabolism; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D006003:Glycogen / Q000032:analysis; D006706:Homeostasis; D007773:Lactates / Q000032:analysis; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009929:Organ Size; D027701:Organic Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics; D000074058:Solute Carrier Family 22 Member 5
chemical_list: D007773:Lactates; D027701:Organic Cation Transport Proteins; C492019:Slc22a5 protein, mouse; D000074058:Solute Carrier Family 22 Member 5; D000255:Adenosine Triphosphate; D006003:Glycogen; D002331:Carnitine; D020155:3-Hydroxybutyric Acid