Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy.
Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy.
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DOI：
10.3389/fphys.2023.1283674
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发表时间：
2023
影响因子：
4
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中科院分区：
文献类型：
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FOLFOX（5-氟尿嘧啶，亚叶酸，奥沙利铂）化疗是一种治疗结直肠癌的方法，可引起持续性疲劳和代谢功能障碍。化疗停止后定期运动被广泛推荐给癌症患者，并已被证明可以提高小鼠的抗疲劳能力。然而，在了解早期全身和骨骼肌对定期运动的适应是否因既往FOLFOX化疗治疗而改变方面仍存在差距。此外，运动持续时间对早期代谢和骨骼肌转录适应的影响尚未完全确定。 目的：研究既往FOLFOX化疗治疗对反复短期或长期跑台运动早期适应的影响，包括雄性小鼠循环代谢调节因子、骨骼肌COXIV活性和肌因子/运动因子基因表达的空腹调节。 方法：雄性C57 BL 6/J小鼠完成4个周期的FOLFOX或PBS，并允许恢复4周。小鼠亚组进行了14次（6天/周，18米/分钟，5%级）的短期（10分钟/天）或长期（55分钟/天）的跑步机运动。在最后一次运动后48-72 h收集血浆和肌肉组织用于生化分析。 结果如下：长时间运动增加了健康PBS小鼠的空腹血浆骨钙素、LIF和IL-6，这些变化可通过先前的FOLFOX治疗消除。在PBS小鼠中，缓慢氧化的比目鱼肌COXIV活性响应于长时间运动而增加，这被先前的FOLFOX治疗阻断。快速糖酵解跖肌COXIV活性增加与FOLFOX给药无关的短期运动。长期运动的主要作用是增加空腹肌肉IL-6和COXIV mRNA表达，与FOLFOX无关。FOLFOX给药降低了肌肉IL-6、LIF和BDNF mRNA的表达，与长期运动无关。有趣的是，短时间运动抑制了FOLXOX对肌肉肌生长抑制素mRNA表达的诱导。 结论：FOLFOX减弱了与空腹循环骨钙素、LIF和IL-6相关的早期运动适应。然而，既往FOLFOX治疗并未改变跖肌COXIV活性和血浆脂联素的运动适应性。对化疗后运动适应机制的进一步理解将为成功治疗癌症幸存者的疲劳和代谢功能障碍提供基础。
FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is a treatment for colorectal cancer that can induce persistent fatigue and metabolic dysfunction. Regular exercise after chemotherapy cessation is widely recommended for cancer patients and has been shown to improve fatigue resistance in mice. However, gaps remain in understanding whether the early systemic and skeletal muscle adaptations to regular exercise are altered by prior FOLFOX chemotherapy treatment. Furthermore, the effects of exercise duration on early metabolic and skeletal muscle transcriptional adaptations are not fully established. Purpose: Investigate the effects of prior FOLFOX chemotherapy treatment on the early adaptations to repeated short- or long-duration treadmill exercise, including the fasting regulation of circulating metabolic regulators, skeletal muscle COXIV activity and myokine/exerkine gene expression in male mice. Methods: Male C57BL6/J mice completed 4 cycles of FOLFOX or PBS and were allowed to recover for 4-weeks. Subsets of mice performed 14 sessions (6 d/wk, 18 m/min, 5% grade) of short- (10 min/d) or long-duration (55 min/d) treadmill exercise. Blood plasma and muscle tissues were collected 48–72 h after the last exercise bout for biochemical analyses. Results: Long-duration exercise increased fasting plasma osteocalcin, LIF, and IL-6 in healthy PBS mice, and these changes were ablated by prior FOLFOX treatment. Slow-oxidative soleus muscle COXIV activity increased in response to long-duration exercise in PBS mice, which was blocked by prior FOLFOX treatment. Fast-glycolytic plantaris muscle COXIV activity increased with short-duration exercise independent of FOLFOX administration. There was a main effect for long-duration exercise to increase fasting muscle IL-6 and COXIV mRNA expression independent of FOLFOX. FOLFOX administration reduced muscle IL-6, LIF, and BDNF mRNA expression irrespective of long-duration exercise. Interestingly, short-duration exercise suppressed the FOLXOX induction of muscle myostatin mRNA expression. Conclusion: FOLFOX attenuated early exercise adaptations related to fasting circulating osteocalcin, LIF, and IL-6. However, prior FOLFOX treatment did not alter the exercise adaptations of plantaris muscle COXIV activity and plasma adiponectin. An improved understanding of mechanisms underlying exercise adaptations after chemotherapy will provide the basis for successfully treating fatigue and metabolic dysfunction in cancer survivors.
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影响因子：
5.2
作者：
Chung, Eric;Lee, Hye Sun;Kang, Jeonghyun
通讯作者：
Kang, Jeonghyun
影响因子：
7.7
作者：
Febbraio, MA;Hiscock, N;Pedersen, BK
通讯作者：
Pedersen, BK
影响因子：
5.8
作者：
Hellsten, Ylva;Nyberg, Michael
通讯作者：
Nyberg, Michael
影响因子：
29
作者：
Goodpaster BH;Sparks LM
通讯作者：
Sparks LM
影响因子：
--
作者：
HENRIKSSON, J;CHI, MMY;LOWRY, OH
通讯作者：
LOWRY, OH