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

View Article: PubMed Central

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.

No MeSH data available.


Related in: MedlinePlus

Oxidation rate of palmitoyl-CoA (C16-CoA) (A) and gene expression of fatty acid dehydrogenases [MCAD (B), LCAD (C) and AOX (D)]. White and black bars represent WT and VLCAD-/- mice, respectively. Values are represented as mean ± SEM (n = 5-6).* indicates significant differences between WT and VLCAD-/- mice within an experimental set. # indicates significant differences between WT or VLCAD-/- mice under different stress conditions as compared to resting mice. * and # values were considered significant if p < 0.05 (Two way ANOVA with Bonferroni correction and Student’s t-test).
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Fig1: Oxidation rate of palmitoyl-CoA (C16-CoA) (A) and gene expression of fatty acid dehydrogenases [MCAD (B), LCAD (C) and AOX (D)]. White and black bars represent WT and VLCAD-/- mice, respectively. Values are represented as mean ± SEM (n = 5-6).* indicates significant differences between WT and VLCAD-/- mice within an experimental set. # indicates significant differences between WT or VLCAD-/- mice under different stress conditions as compared to resting mice. * and # values were considered significant if p < 0.05 (Two way ANOVA with Bonferroni correction and Student’s t-test).

Mentions: 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. As shown in Figure 1A, under resting condition, the turnover rate in VLCAD−/− mice was significantly reduced by 20% in mutants as compared to the littermates. Interestingly, 1 h on the treadmill did not affect the oxidation capacity of the VLCAD−/− mice, whereas a training protocol over 2 weeks significantly reduced the turnover rate of C16-CoA in the VLCAD−/− mice as compared to sedentary mutants (9 ± 0.49 vs. 13.1 ± 0.54 mU/mg). A similar significant reduction of C16-CoA oxidation capacity was also observed after 24 h of fasting in both genotypes, as shown in Figure 1. Fasting, therefore, did not result in a genotype-specific effect in contrast to long-term physical exercise.Figure 1


Renal response to short- and long-term exercise in very-long-chain acyl-CoA dehydrogenase-deficient (VLCAD − / − ) mice
Oxidation rate of palmitoyl-CoA (C16-CoA) (A) and gene expression of fatty acid dehydrogenases [MCAD (B), LCAD (C) and AOX (D)]. White and black bars represent WT and VLCAD-/- mice, respectively. Values are represented as mean ± SEM (n = 5-6).* indicates significant differences between WT and VLCAD-/- mice within an experimental set. # indicates significant differences between WT or VLCAD-/- mice under different stress conditions as compared to resting mice. * and # values were considered significant if p < 0.05 (Two way ANOVA with Bonferroni correction and Student’s t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530567&req=5

Fig1: Oxidation rate of palmitoyl-CoA (C16-CoA) (A) and gene expression of fatty acid dehydrogenases [MCAD (B), LCAD (C) and AOX (D)]. White and black bars represent WT and VLCAD-/- mice, respectively. Values are represented as mean ± SEM (n = 5-6).* indicates significant differences between WT and VLCAD-/- mice within an experimental set. # indicates significant differences between WT or VLCAD-/- mice under different stress conditions as compared to resting mice. * and # values were considered significant if p < 0.05 (Two way ANOVA with Bonferroni correction and Student’s t-test).
Mentions: 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. As shown in Figure 1A, under resting condition, the turnover rate in VLCAD−/− mice was significantly reduced by 20% in mutants as compared to the littermates. Interestingly, 1 h on the treadmill did not affect the oxidation capacity of the VLCAD−/− mice, whereas a training protocol over 2 weeks significantly reduced the turnover rate of C16-CoA in the VLCAD−/− mice as compared to sedentary mutants (9 ± 0.49 vs. 13.1 ± 0.54 mU/mg). A similar significant reduction of C16-CoA oxidation capacity was also observed after 24 h of fasting in both genotypes, as shown in Figure 1. Fasting, therefore, did not result in a genotype-specific effect in contrast to long-term physical exercise.Figure 1

View Article: PubMed Central

ABSTRACT

Background: Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) is the most common disorder of mitochondrial &beta;-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&minus;/&minus; mice under different metabolic conditions such as after moderate (1&nbsp;h) and intensive long-term (1&nbsp;h twice per day over 2&nbsp;weeks) physical exercise and after 24&nbsp;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&minus;/&minus; mice fully compensates for impaired fatty acid oxidation by enhanced glycogen utilization and preserves renal energy metabolism and function.

No MeSH data available.


Related in: MedlinePlus