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.

中文翻译：

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极长链酰基辅酶A脱氢酶缺陷（VLCAD-/-）小鼠对短期和长期运动的肾脏反应

背景极长链酰基辅酶A脱氢酶（VLCAD）缺乏是长链脂肪酸线粒体β-氧化最常见的疾病。为了维持葡萄糖稳态，肾脏和肝脏作为主要的糖异生器官在脂肪酸氧化受损的情况下发挥重要作用。然而，关于有缺陷的脂肪酸氧化机制如何影响肾脏代谢和功能以及肾脏能量供应，尤其是在分解代谢情况下，我们知之甚少。 h) 和长期强化（2 周内每天两次 1 小时）体育锻炼和禁食 24 小时后。我们测量了棕榈酰辅酶 A (C16-CoA) 的氧化速率以及参与脂肪生成和肾功能衰竭的基因的表达。通过抗氧化酶的功能评估氧化应激。此外，我们量化了肾脏中糖原和长链酰基肉碱的含量。 结果我们观察到肾糖原的显着消耗伴随长链酰基肉碱的减少，表明能量产生的底物转换和受损脂肪酸的最佳补偿肾脏氧化。事实上，突变体在分解代谢条件下没有表现出任何氧化应激或肾功能衰竭的迹象。结论我们的数据表明，尽管 Acadvl 消融，