title: Renal response to short- and long-term exercise in very-long-chain acyl-CoA dehydrogenase-deficient (VLCAD(-/-)) mice.
abstract: BACKGROUND
  Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial β-oxidation of long-chain fatty acids. In order to maintain glucose homeostasis, the kidney and liver as the main gluconeogenic organs play an important role under conditions of impaired fatty acid oxidation. However, little is known about how a defective fatty acid oxidation machinery affects renal metabolism and function as well as renal energy supply especially during catabolic situations.
  
  
  METHODS
  In this study, we analyzed VLCAD(-/-) mice under different metabolic conditions such as after moderate (1 h) and intensive long-term (1 h twice per day over 2 weeks) physical exercise and after 24 h of fasting. We measured the oxidation rate of palmitoyl-CoA (C16-CoA) as well as the expression of genes involved in lipogenesis and renal failure. Oxidative stress was assessed by the function of antioxidant enzymes. Moreover, we quantified the content of glycogen and long-chain acylcarnitines in the kidney.
  
  
  RESULTS
  We observed a significant depletion in renal glycogen with a concomitant reduction in long-chain acylcarnitines, suggesting a substrate switch for energy production and an optimal compensation of impaired fatty acid oxidation in the kidney. In fact, the mutants did not show any signs of oxidative stress or renal failure under catabolic conditions.
  
  
  CONCLUSIONS
  Our data demonstrate that despite Acadvl ablation, the kidney of VLCAD(-/-) mice fully compensates for impaired fatty acid oxidation by enhanced glycogen utilization and preserves renal energy metabolism and function.
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Mathildenstrasse 1, Freiburg, 79106, Germany. sara.tucci@uniklinik-freiburg.de.
authors.forename: Sara
authors.initials: S
authors.lastname: Tucci
authors.affiliation: Department of General Pediatrics, Neonatology and Children's Cardiology, University Children's Hospital, Duesseldorf, 40225, Germany. antoniakrogmann@gmx.de.
authors.forename: Antonia
authors.initials: A
authors.lastname: Krogmann
authors.affiliation: Department of General Pediatrics, Neonatology and Children's Cardiology, University Children's Hospital, Duesseldorf, 40225, Germany. Herebian@med.uni-duesseldorf.de.
authors.forename: Diran
authors.initials: D
authors.lastname: Herebian
authors.affiliation: Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Mathildenstrasse 1, Freiburg, 79106, Germany. ute.spiekerkoetter@uniklinik-freiburg.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Spiekerkoetter
keywords: Acylcarnitines; Fatty acid oxidation; Glucose homeostasis; Oxidative stress; VLCAD deficiency