Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease.

Skeletal muscle metabolic responses to physical activity are muscle type specific in a rat model of chronic kidney disease.
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DOI:
10.1038/s41598-021-89120-8
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发表时间:
2021-05-07
期刊:
影响因子:
4.6
通讯作者:
O'Connell TM
O'Connell TM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Avin KG;Hughes MC;Chen NX;Srinivasan S;O'Neill KD;Evan AP;Bacallao RL;Schulte ML;Moorthi RN;Gisch DL;Perry CGR;Moe SM;O'Connell TM

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慢性肾脏疾病(CKD)导致肌肉骨骼损伤,受肌肉代谢的影响。我们在慢性肾脏病大鼠模型中检验了10周自愿轮跑可以改善骨骼肌线粒体活性和功能的假设。各组包括(n = 12-14/组):(1)正常同窝仔(NL);(2)CKD;和(3)CKD-10周自愿轮跑(CKD-W)。在35周龄时,在比目鱼肌和趾长伸肌(EDL)中进行以下测定:靶向代谢组学、线粒体呼吸和蛋白质表达。氨基酸相关化合物在CKD肌肉中减少,并且不能通过体力活动恢复。与NL相比,CKD比目鱼肌的线粒体呼吸增加,但不受体力活动的影响。NL组和CKD组的EDL呼吸无明显差异,但CKD-轮大鼠的呼吸较CKD组和NL组增加。我们的研究结果表明,比目鱼肌可能更容易受到CKD诱导的线粒体复合物含量和呼吸的变化,而在EDL中,这些变化是响应轻度体力活动引起的生理负荷。未来的研究应该集中在改善两种类型肌肉中线粒体功能的治疗方法上,以确定这种治疗方法是否可以提高CKD患者适应体力活动的能力。
Chronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12–14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.
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