High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content
High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content
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DOI：
10.1074/jbc.m206726200
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发表时间：
2002-11-08
影响因子：
4.8
通讯作者：
Bouillaud, F
中科院分区：
文献类型：
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作者：
Couplan, E;Gelly, C;Bouillaud, F
棕色脂肪组织的线粒体解偶联蛋白（UCP1）在转基因小鼠的骨骼肌和心脏中表达，其表达水平与棕色脂肪组织线粒体中的表达水平相当。这些转基因小鼠的体重较低，与体重相关时，食物摄入量和能量消耗增加。观察到肌肉质量的特定减少，但根据肌肉的收缩活动而变化。心脏和比目鱼肌不受影响，这表明进行定期收缩的肌肉因此能够持续产生线粒体 ATP，受到保护。相比之下，腓肠肌和跖肌显示出质量严重减少，纤维类型从快到慢的转变，主要促进 IIa 和 IIx：纤维以最快的和糖酵解的 IIb 型纤维为代价。这些观察结果被解释为 UCP1 质子传递活性的强烈电势依赖性的结果，这确保了当线粒体 ATP 产生强烈时观察到的膜电势处的质子泄漏可以忽略不计。因此，UCP1 对于线粒体 ATP 的大量产生并无害处，这解释了心脏对 UCP1 高表达水平的耐受性。在休息时的肌肉中，ATP 生成量较低，膜电位的上升会增强 UCP1 的活性。通过 UCP1 的质子返回模拟了持续产生 ATP 的效果，永久降低线粒体膜电位。这很可能构成导致静止纤维类型转变的信号来源。
The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles. Heart and soleus muscle are unaffected, indicating that muscles undergoing regular contractions, and therefore with a continuous mitochondrial ATP production, are protected. In contrast, the gastrocnemius and plantaris muscles showed a severely reduced mass and a fast to slow shift in fiber types promoting mainly IIa and IIx: fibers at the expense of fastest and glycolytic type IIb fibers. These observations are interpreted as a consequence of the strong potential dependence of the UCP1 protonophoric activity, which ensures a negligible proton leak at the membrane potential observed when mitochondrial ATP production is intense. Therefore UCP1 is not deleterious for an intense mitochondrial ATP production and this explains the tolerance of the heart to a high expression level of UCP1. In muscles at rest, where ATP production is low, the rise in membrane potential enhances UCP1 activity. The proton return through UCP1 mimics the effect of a sustained ATP production, permanently lowering mitochondrial membrane potential. This very likely constitutes the origin of the signal leading to the transition in fiber types at rest.