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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >The mitochondrial metabolic reprogramming agent trimetazidine as an ?￠????exercise mimetic?￠???? in cachectic C26-bearing mice
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The mitochondrial metabolic reprogramming agent trimetazidine as an ?￠????exercise mimetic?￠???? in cachectic C26-bearing mice

机译：线粒体代谢重编程剂曲美他嗪为“模拟运动”。在带有恶病质C26的小鼠中

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Abstract Background Cancer cachexia is characterized by muscle depletion and exercise intolerance caused by an imbalance between protein synthesis and degradation and by impaired myogenesis. Myofibre metabolic efficiency is crucial so as to assure optimal muscle function. Some drugs are able to reprogram cell metabolism and, in some cases, to enhance metabolic efficiency. Based on these premises, we chose to investigate the ability of the metabolic modulator trimetazidine (TMZ) to counteract skeletal muscle dysfunctions and wasting occurring in cancer cachexia. Methods For this purpose, we used mice bearing the C26 colon carcinoma as a model of cancer cachexia. Mice received 5 mg/kg TMZ (i.p.) once a day for 12 consecutive days. A forelimb grip strength test was performed and tibialis anterior , and gastrocnemius muscles were excised for analysis. Ex vivo measurement of skeletal muscle contractile properties was also performed. Results Our data showed that TMZ induces some effects typically achieved through exercise, among which is grip strength increase, an enhanced fast-to slow myofibre phenotype shift, reduced glycaemia, PGC1???± up-regulation, oxidative metabolism, and mitochondrial biogenesis. TMZ also partially restores the myofibre cross-sectional area in C26-bearing mice, while modulation of autophagy and apoptosis were excluded as mediators of TMZ effects. Conclusions In conclusion, our data show that TMZ acts like an ?￠????exercise mimetic?￠???? and is able to enhance some mechanisms of adaptation to stress in cancer cachexia. This makes the modulation of the metabolism, and in particular TMZ, a suitable candidate for a therapeutic rehabilitative protocol design, particularly considering that TMZ has already been approved for clinical use.
机译：摘要背景恶性肿瘤恶病质的特征是由于蛋白质合成与降解之间的不平衡以及肌生成障碍导致的肌肉衰竭和运动不耐症。肌纤维代谢效率对于确保最佳的肌肉功能至关重要。一些药物能够重新编程细胞代谢，并且在某些情况下可以提高代谢效率。基于这些前提，我们选择研究代谢调节剂曲美他嗪（TMZ）抵抗骨骼肌功能障碍和癌症恶病质中浪费的能力。方法为此，我们使用了带有C26结肠癌的小鼠作为癌症恶病质的模型。小鼠连续12天每天接受5 mg / kg TMZ（i.p.）。进行前肢握力测试，并切除胫骨前和腓肠肌进行分析。还进行了骨骼肌收缩特性的离体测量。结果我们的数据表明，TMZ诱导了一些通常通过运动获得的效果，其中包括抓地力的增强，肌纤维表型从快到慢的增强，血糖降低，PGC1α±上调，氧化代谢和线粒体生物发生。 TMZ还可以部分恢复C26小鼠的肌纤维横截面积，而自噬和细胞凋亡的调节被排除为TMZ效应的介质。结论总之，我们的数据表明TMZ就像一个“模拟运动”。并能够增强某些适应癌症恶病质压力的机制。这使得新陈代谢的调节，尤其是TMZ成为治疗性康复方案设计的合适候选者，特别是考虑到TMZ已被批准用于临床。

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