title: Hepatic and muscular effects of different dietary fat content in VLCAD deficient mice.
abstract: BACKGROUND
  Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common long-chain fatty acid oxidation defect presenting with heterogeneous clinical phenotypes. Dietary fat plays a crucial role in disease pathogenesis and fat restriction is a common treatment measure. We here investigate the hepatic and muscular effects of a fat-enriched and a fat-restricted diet.
  
  
  METHODS
  VLCAD knock-out (KO) and wild-type (WT) mice are subjected to a fat-rich (10.6%), a fat-reduced (2.6%) or a regular mouse diet (5.1%) for 5 weeks. Analyses are performed at rest and after one hour exercise on a treadmill. Acylcarnitines in muscle as well as lipid and glycogen content in muscle and liver are quantified. Expression of genes involved in lipogenesis is measured by Real-Time-PCR.
  
  
  RESULTS
  At rest, VLCAD KO mice develop no clinical phenotype with all three diets, but importantly VLCAD KO mice cannot perform one hour exercise as compared to WT, this is especially apparent in mice with a fat-reduced diet. Moreover, changes in dietary fat content induce a significant increase in muscular long-chain acylcarnitines and hepatic lipid content in VLCAD KO mice after exercise. A fat-reduced diet up-regulates hepatic lipogenesis at rest. At the same time, muscular glycogen is significantly lower than in WT.
  
  
  CONCLUSIONS
  We here demonstrate that a fat-reduced and carbohydrate-enriched diet does not prevent the myopathic phenotype in VLCAD KO mice. An increase in dietary fat is safe at rest with respect to the muscle but results in a significant muscular acylcarnitine increase after exercise.
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Duesseldorf, Germany. Sonja.Primassin@med.uni-duesseldorf.de
authors.forename: Sonja
authors.initials: S
authors.lastname: Primassin
authors.forename: Sara
authors.initials: S
authors.lastname: Tucci
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D000080984:Congenital Bone Marrow Failure Syndromes; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D004734:Energy Metabolism; D006003:Glycogen / Q000378:metabolism; D050356:Lipid Metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D028361:Mitochondrial Diseases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism*; D005082:Physical Exertion; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D008055:Lipids; C116917:acylcarnitine; D006003:Glycogen; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine