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Abstract：
In general, metabolic flexibility refers to an organism\'s capacity to adapt to metabolic changes due to differing energy demands. The aim of this work is to summarize and discuss recent findings regarding variables that modulate energy regulation in two different pathways of mitochondrial fatty metabolism: β-oxidation and fatty acid biosynthesis. We focus specifically on two diseases: very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and malonyl-CoA synthetase deficiency (acyl-CoA synthetase family member 3 (ACSF3)) deficiency, which are both characterized by alterations in metabolic flexibility. On the one hand, in a mouse model of VLCAD-deficient (VLCAD-/-) mice, the white skeletal muscle undergoes metabolic and morphologic transdifferentiation towards glycolytic muscle fiber types via the up-regulation of mitochondrial fatty acid biosynthesis (mtFAS). On the other hand, in ACSF3-deficient patients, fibroblasts show impaired mitochondrial respiration, reduced lipoylation, and reduced glycolytic flux, which are compensated for by an increased β-oxidation rate and the use of anaplerotic amino acids to address the energy needs. Here, we discuss a possible co-regulation by mtFAS and β-oxidation in the maintenance of energy homeostasis.
摘要：
总的来说,代谢的灵活性是指生物体适应代谢变化的能力，由于不同的能量需求。这项工作的目的是总结和讨论有关调节线粒体脂肪代谢两种不同途径中能量调节的变量的最新发现：β-氧化和脂肪酸生物合成。我们特别关注两种疾病：非常长链酰基辅酶A脱氢酶缺乏症（VLCADD）和丙二酰辅酶A合成酶缺乏症（酰基辅酶A合成酶家族成员3（ACSF3））缺乏症，两者的特征都是代谢灵活性的改变。一方面,在VLCAD缺陷（VLCAD-/-）小鼠的小鼠模型中，通过线粒体脂肪酸生物合成(mtFAS)的上调,白色骨骼肌经历向糖酵解肌纤维类型的代谢和形态转分化.另一方面,在缺乏ACSF3的患者中，成纤维细胞显示线粒体呼吸受损，减少的脂肪化，减少糖酵解通量，通过增加的β氧化速率和使用回补氨基酸来满足能源需求来弥补。这里,我们讨论了mtFAS和β-氧化在维持能量稳态中可能的共同调节。
