Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia
Aerobic and resistance training dependent skeletal muscle plasticity in the colon-26 murine model of cancer cachexia
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DOI：
10.1016/j.metabol.2016.01.014
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发表时间：
2016-05-01
影响因子：
9.8
通讯作者：
Kim, Jeong-Su
中科院分区：
文献类型：
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作者：
Khamoui, Andy V.;Park, Bong-Sup;Kim, Jeong-Su
目的.癌症恶病质的适当运动训练模式尚未建立。使用结肠癌26（C26）小鼠模型的癌症恶病质，我们定义和比较骨骼肌反应有氧和阻力训练。最初将10个月大的Balb/c小鼠分配到对照、有氧训练（AT;轮跑）或阻力训练（RT;爬梯）（n = 16-17/组）。在8周的训练后，每组中的一半被注射C26肿瘤细胞，然后再进行3周的训练。身体成分和神经肌肉功能进行了评估前和训练后。在训练后收集肌肉并分析纤维横截面积（CSA）、Akt mTOR信号、胰岛素样生长因子-I（IGF-I）和生肌调节因子的表达。C26（-8%）、AT + C26（-18%）和RT + C26（-15%）中的总体重降低（p < 0.05），但对照没有。感觉运动功能在对照（-16%）、C26（-13%）和RT + C26（-23%）中下降（p < 0.05），但AT + C26没有。类似地，对照组（-7%）、C26组（-21%）和RT + C26组（-10%）的强度/体重降低（p < 0.05），但AT + C26组未降低。AT + C26组的腓肠肌质量/体重往往大于C26组（+6%，p = 0.09）。在AT + C26中部分校正了脾脏的膨胀（-27% vs. C26，p < 0.05）。所有C26组的纤维CSA均低于对照组（-32%至46%，p < 0.05）;然而，根据C26和AT + C26计算的效应量较大（+24%，d = 1.04）。AT + C26中mTOR的磷酸化水平超过C26（+32%，p < 0.05）。与对照组相比，RT + C26显示IGF-IEa（+79%）和肌细胞生成素（+126%）的mRNA表达更高（p < 0.05），IGF-IEb（+127%，p = 0.069）更高的趋势更强。有氧或阻力训练不能防止肿瘤引起的体重减轻。然而，有氧训练可能保留了功能，减少了脾脏的炎症反应，并可能通过激活mTOR略微挽救了肌肉质量。因此有氧训练可能对癌症恶病质患者有治疗价值。相反，阻力训练诱导了与肌肉损伤和修复相关的基因的表达。这种基因反应可能支持荷瘤状态下高抵抗负荷产生的过度压力。(C)2016 Elsevier Inc. All rights reserved.
Purpose. The appropriate mode of exercise training for cancer cachexia is not well established. Using the colon-26 (C26) mouse model of cancer cachexia, we defined and compared the skeletal muscle responses to aerobic and resistance training.Methods. Twelve-month old Balb/c mice were initially assigned to control, aerobic training (AT; wheel running), or resistance training (RT; ladder climbing) (n = 16-17/group). After 8 weeks of training, half of each group was injected with C26 tumor cells, followed by 3 additional weeks of training. Body composition and neuromuscular function was evaluated pre- and post-training. Muscles were collected post-training and analyzed for fiber cross-sectional area (CSA), Akt mTOR signaling, and expression of insulin-like growth factor-I (IGF-I) and myogenic regulatory factors.Results. Total body mass decreased (p < 0.05) in C26 (-8%), AT + C26 (-18%), and RT + C26 (-15%) but not control. Sensorimotor function declined (p < 0.05) in control (-16%), C26 (-13%), and RT + C26 (-23%) but not AT + C26. Similarly, strength/body weight decreased (p < 0.05) in control (-7%), C26 (-21%), and RT + C26 (-10%) but not AT + C26. Gastrocnemius mass/body weight tended to be greater in AT + C26 vs. C26 (+6%, p = 0.09). Enlargement of the spleen was partially corrected in AT + C26 (-27% vs. C26, p < 0.05). Fiber CSA was lower in all C26 groups vs. control (-32% to 46%, p < 0.05); however, the effect size calculated from C26 and AT + C26 was large (+24%, d = 1.04). Phosphorylated levels of mTOR in AT + C26 exceeded C26 (+32%, p < 0.05). RT + C26 showed greater mRNA expression (p < 0.05) of IGF-IEa (+79%) and myogenin (+126%) with a strong tendency for greater IGF-IEb (+127%, p = 0.069) vs. control.Conclusions. Aerobic or resistance training was unable to prevent tumor-induced body weight loss. However, aerobic training may have preserved function, reduced the inflammatory response of the spleen, and marginally rescued muscle mass possibly through activation of mTOR. Aerobic training may therefore have therpeutic value for patients with cancer cachexia. In contrast, resistance training induced the expression of genes associated with muscle damage and repair. This gene response may be supportive of excessive stress generated by high resistance loading in a tumor-bearing state. (C) 2016 Elsevier Inc. All rights reserved.