Skeletal muscle undergoes fiber type metabolic switch without myosin heavy chain switch in response to defective fatty acid oxidation.
Skeletal muscle undergoes fiber type metabolic switch without myosin heavy chain switch in response to defective fatty acid oxidation.
复制标题
骨骼肌经历纤维型代谢转换，而没有肌球蛋白重链转换，以响应缺陷的脂肪酸氧化。
DOI：
10.1016/j.molmet.2022.101456
复制
发表时间：
2022-05
影响因子：
8.1
通讯作者：
Ellis JM
中科院分区：
文献类型：
--
作者：
Pereyra AS;Lin CT;Sanchez DM;Laskin J;Spangenburg EE;Neufer PD;Fisher-Wellman K;Ellis JM
骨骼肌是一种异质的动态组织，通过调节肌纤维的大小和类型来适应功能需求和底物可用性。肌纤维类型的概念与其收缩（慢或快）和代谢（糖酵解或氧化）特性有关。在这里，我们测试了肌肉氧化catalysts中断是否足以促使并行适应能量和收缩蛋白质组成。由于肉毒碱棕榈酰转移酶2（Cpt 2Sk-/-）的缺失而导致骨骼肌线粒体长链脂肪酸氧化缺陷（mLCFAO）的小鼠用于模拟肌肉宏量营养素分解代谢的转变。比较了Cpt 2Sk −/−小鼠和对照同窝小鼠的糖酵解和氧化肌肉的能量代谢相关蛋白表达、线粒体呼吸能力和肌球蛋白重链亚型组成。控制肌肉之间的能量需求的生物能量学和宏量营养素利用的差异是线粒体固有的，从而可以明确区分肌肉类型。CPT 2的缺失消融了mLCFAO，并导致线粒体生物合成主要发生在氧化肌纤维中。Cpt 2Sk −/−氧化肌肉的代谢相关蛋白质组特征与糖酵解肌肉比对照氧化肌肉更相似。相应地，CPT 2缺乏的氧化肌肉的内在底物支持的线粒体呼吸转移到密切匹配的糖酵解肌肉。尽管线粒体代谢发生了这种变化，但根据肌球蛋白重链组成分析，CPT 2缺失不会导致基于收缩的纤维类型转换。线粒体长链脂肪酸氧化的损失，elyphan的适应性反应，涉及氧化的肌肉向类似于糖酵解肌肉的代谢谱的转换，但这并不伴随着肌球蛋白重链亚型的变化。这些数据表明，在肌肉catastrophic的变化不足以驱动在收缩装置的变化，但足以驱动代谢特性的适应性变化。糖酵解中的燃料氧化与氧化性肌肉相比是不同的，并且是线粒体固有的。肌肉CPT 2损失eleventh纤维型依赖的线粒体生物合成。肌肉CPT 2损失导致线粒体和代谢特性的氧化-糖酵解转变。肌肉CPT 2缺失不改变肌球蛋白重链亚型组成。CPT 2缺乏的肌肉表现出代谢-收缩装置不匹配。
Skeletal muscle is a heterogeneous and dynamic tissue that adapts to functional demands and substrate availability by modulating muscle fiber size and type. The concept of muscle fiber type relates to its contractile (slow or fast) and metabolic (glycolytic or oxidative) properties. Here, we tested whether disruptions in muscle oxidative catabolism are sufficient to prompt parallel adaptations in energetics and contractile protein composition. Mice with defective mitochondrial long-chain fatty acid oxidation (mLCFAO) in the skeletal muscle due to loss of carnitine palmitoyltransferase 2 (Cpt2Sk−/−) were used to model a shift in muscle macronutrient catabolism. Glycolytic and oxidative muscles of Cpt2Sk−/− mice and control littermates were compared for the expression of energy metabolism-related proteins, mitochondrial respiratory capacity, and myosin heavy chain isoform composition. Differences in bioenergetics and macronutrient utilization in response to energy demands between control muscles were intrinsic to the mitochondria, allowing for a clear distinction of muscle types. Loss of CPT2 ablated mLCFAO and resulted in mitochondrial biogenesis occurring most predominantly in oxidative muscle fibers. The metabolism-related proteomic signature of Cpt2Sk−/− oxidative muscle more closely resembled that of glycolytic muscle than of control oxidative muscle. Respectively, intrinsic substrate-supported mitochondrial respiration of CPT2 deficient oxidative muscles shifted to closely match that of glycolytic muscles. Despite this shift in mitochondrial metabolism, CPT2 deletion did not result in contractile-based fiber type switching according to myosin heavy chain composition analysis. The loss of mitochondrial long-chain fatty acid oxidation elicits an adaptive response involving conversion of oxidative muscle toward a metabolic profile that resembles a glycolytic muscle, but this is not accompanied by changes in myosin heavy chain isoforms. These data suggest that shifts in muscle catabolism are not sufficient to drive shifts in the contractile apparatus but are sufficient to drive adaptive changes in metabolic properties. Fuel oxidation in glycolytic compared to oxidative muscles are different and intrinsic to the mitochondria. Muscle CPT2 loss elicits fiber-type dependent mitochondrial biogenesis. Muscle CPT2 loss elicits an oxidative-to-glycolytic shift in mitochondrial and metabolic properties. Muscle CPT2 loss does not alter myosin heavy chain isoform composition. CPT2 deficient muscles demonstrate a metabolic-contractile apparatus mismatch.
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影响因子：
3
作者：
Bardou P;Mariette J;Escudié F;Djemiel C;Klopp C
通讯作者：
Klopp C
影响因子：
4.6
作者：
McLaughlin KL;Hagen JT;Coalson HS;Nelson MAM;Kew KA;Wooten AR;Fisher-Wellman KH
通讯作者：
Fisher-Wellman KH
影响因子：
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作者：
Lesack K;Naugler C
通讯作者：
Naugler C
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
影响因子：
4.4
作者：
Lang, Franziska;Khaghani, Solmaz;Krueger, Marcus
通讯作者：
Krueger, Marcus