The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function
The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function
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DOI：
10.1113/expphysiol.2012.070037
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发表时间：
2013-04-01
影响因子：
2.7
通讯作者：
Lundby, Carsten
中科院分区：
文献类型：
--
作者：
Jacobs, Robert A.;Diaz, Victor;Lundby, Carsten
新发现中心点 这项研究的中心问题是什么？小鼠骨骼肌线粒体是否与人类骨骼肌线粒体足够相似，可以作为合适的模型？骨骼肌类型的差异如何影响比较？中心点 主要发现及其重要性是什么？我们发现小鼠骨骼肌的呼吸能力和控制功能与人类非常相似。股外侧肌，总体上与小鼠股四头肌最相似。然而，这种相似性并不普遍，因为 I 型小鼠肌肉脂肪氧化过程中电子传递的耦合控制与人类股外侧肌更具相似性。不同类型的骨骼肌之间是否存在线粒体功能差异以及小鼠骨骼肌线粒体功能是否可以作为人类骨骼肌线粒体功能的有效模型尚存在争议。本研究的目的是比较和对比三种不同的小鼠骨骼肌，并确定与人类骨骼肌呼吸能力和控制最相似的小鼠肌肉。小鼠股四头肌 (QUADM)、比目鱼肌 (SOLM) 和腓肠肌 (GASTM) 骨骼肌取自 8 至 10 周大的健康小鼠 (n = 8)，分别代表混合肌、氧化肌和糖酵解肌。还从年轻、活跃、健康的人类受试者 (n = 8) 的股外侧肌 (QUADH) 中采集了骨骼肌样本。使用高分辨率呼吸测量法检查所有骨骼肌样本中的线粒体功能，并通过柠檬酸合酶活性对线粒体含量进行定量。 SOLM 中所有呼吸状态下的质量特异性呼吸均高于 GASTM 和 QUADH (P < 0.01)。然而，当控制线粒体含量时，SOLM 呼吸低于 GASTM 和 QUADH（分别为 P < 0.05 和 P < 0.01）。当比较小鼠和人类肌肉的呼吸能力时，QUADM 与 QUADH 相比仅表现出一种不同的呼吸状态。这些结果表明，当呼吸能力根据线粒体含量标准化时，不同类型小鼠骨骼肌之间的线粒体功能存在质的差异，并且年轻、健康 QUADM 中的骨骼肌呼吸能力确实与年轻、健康 QUADH 中的骨骼肌呼吸能力非常一致。
New Findings center dot What is the central question of this study? Do mouse skeletal muscle mitochondria resemble human skeletal muscle mitochondria sufficiently to serve as a proper model and how do differences of skeletal muscle type affect the comparison? center dot What is the main finding and its importance? We find that mouse skeletal muscle respiratory capacity and control function rather similar to human m. vastus lateralis, with the mouse quadricep being overall the most similar. This resemblance is not universal, however, because the coupling control of electron transport during fat oxidation in type I murine muscle is more comparable to human vastus lateralis. It is debatable whether differences in mitochondrial function exist across skeletal muscle types and whether mouse skeletal muscle mitochondrial function can serve as a valid model for human skeletal muscle mitochondrial function. The aims of this study were to compare and contrast three different mouse skeletal muscles and to identify the mouse muscle that most closely resembles human skeletal muscle respiratory capacity and control. Mouse quadriceps (QUADM), soleus (SOLM) and gastrocnemius (GASTM) skeletal muscles were obtained from 8- to 10-week-old healthy mice (n= 8), representing mixed, oxidative and glycolytic muscle, respectively. Skeletal muscle samples were also collected from young, active, healthy human subjects (n= 8) from the vastis lateralis (QUADH). High-resolution respirometry was used to examine mitochondrial function in all skeletal muscle samples, and mitochondrial content was quantified with citrate synthase activity. Mass-specific respiration was higher across all respiratory states in SOLMversus both GASTM and QUADH (P < 0.01). When controlling for mitochondrial content, however, SOLM respiration was lower than GASTM and QUADH (P < 0.05 and P < 0.01, respectively). When comparing respiratory capacity between mouse and human muscle, QUADM exhibited only one different respiratory state when compared with QUADH. These results demonstrate that qualitative differences in mitochondrial function exist between different mouse skeletal muscles types when respiratory capacity is normalized to mitochondrial content, and that skeletal muscle respiratory capacity in young, healthy QUADM does correspond well with that of young, healthy QUADH.