Renal response to short- and long-term exercise in very-long-chain acyl-CoA dehydrogenase-deficient (VLCAD(-/-)) mice.

Sara Tucci,Antonia Krogmann,Ute Spiekerkoetter,Diran Herebian

doi:10.1186/s40348-014-0005-z

Abstract

BackgroundDeficiency 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.MethodsIn 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial β-oxidation of long-chain fatty acids
The symptoms usually manifest in situations of increased energy demand such as fasting, infectious illnesses, and intensive or prolonged physical exercise when the organism relies on fatty acid β-oxidation for energy supply
Turnover rate of palmitoyl-CoA oxidation and gene expression of different dehydrogenases To test whether the oxidation rate in the kidney of VLCAD−/− mice is influenced by increased energy demand or fasting, we measured the turnover rate of C16-CoA in mice during different conditions

Summary

Introduction

Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial β-oxidation of long-chain fatty acids. 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. Deficiency of the very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial β-oxidation of long-chain fatty acids with an incidence of 1:30,000 to 1:100,000 newborns [1,2]. We here investigated how a defective fatty acid oxidation machinery affects kidney function and kidney metabolism with special focus on glucose supply To address this question, we measured the palmitoyl-CoA (C16-CoA) oxidation rate in the kidney of wild-type (WT) and VLCAD−/− mice in situations of normal and increased energy demand as well as the expression of other dehydrogenases with overlapping substrate specificity. Renal glycogen content and acylcarnitines as markers for impaired energy production from fatty acid oxidation were quantified

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