Eicosapentaenoic acid changes muscle transcriptome and intervenes in aging-related fiber type transition in male mice
Eicosapentaenoic acid changes muscle transcriptome and intervenes in aging-related fiber type transition in male mice
复制标题
二十碳五烯酸改变雄性小鼠的肌肉转录组并干预与衰老相关的纤维类型转变
DOI：
10.1152/ajpendo.00184.2020
复制
发表时间：
2021
影响因子：
5.1
通讯作者：
Tanaka Hirotoshi
中科院分区：
文献类型：
--
作者：
Yamazaki Hiroki;Nishimura Mayu;Uehara Masaaki;Kuribara-Souta Akiko;Yamamoto Motohisa;Yoshikawa Noritada;Morohashi Ken-Ichirou;Tanaka Hirotoshi
年龄相关性骨质疏松症与骨骼肌的各种变化有关。这些变化是相互关联的，并与全身新陈代谢有关，然而，其细节在很大程度上是未知的。二十碳五烯酸(EPA)是一种很有前途的抗骨质疏松症的营养素，对全身代谢有多方面的影响。在这项研究中，我们假设骨骼肌的衰老过程可以通过给药EPA进行干预。将75周龄雄性小鼠随机分为两组，分别饲喂不含环境保护剂的饲料(−)和添加1 质量分数的环境保护剂(EPA+)的饲料，持续12 wk。用正常饲料喂养的24周龄雄性小鼠也进行了分析。在基线时，老龄小鼠的握力低于年轻小鼠。12 wk后，与Epa−相比，Epa+表现出相似的肌肉质量，但握力增加。EPA+较EPA−具有更高的胰岛素敏感性。免疫组织化学和肌球蛋白重链(MyHCs)基因表达分析显示，衰老肌肉由快向慢纤维型转变，EPA可部分抑制这一转变。RNA测序(RNA-Seq)分析表明，补充EPA在骨骼肌中发挥路径特异性效应，包括从慢纤维类型向快纤维类型转变的特征。综上所述，我们发现雄性小鼠衰老的骨骼肌表现出较低的握力和纤维类型的变化，这两者都可以被补充EPA抑制，而无论肌肉质量的变化。新与诺特沃特本研究表明，老年雄性小鼠骨骼肌的早期表型以肌肉无力为特征，并伴有从快到慢的纤维型转变，这可以通过饲喂富含EPA的饲料来改善。EPA诱导代谢变化，如全身胰岛素敏感性增加和衰老小鼠肌肉转录组改变。这些变化可能与纤维类型转换有关，并影响肌肉质量。
Age-related sarcopenia is associated with a variety of changes in skeletal muscle. These changes are interrelated with each other and associated with systemic metabolism, the details of which, however, are largely unknown. Eicosapentaenoic acid (EPA) is a promising nutrient against sarcopenia and has multifaceted effects on systemic metabolism. In this study, we hypothesized that the aging process in skeletal muscle can be intervened by the administration of EPA. Seventy-five-week-old male mice were assigned to groups fed an EPA-deprived diet (EPA−) or an EPA-enriched diet with 1 wt% EPA (EPA+) for 12 wk. Twenty-four-week-old male mice fed with normal chow were also analyzed. At baseline, the grip strength of the aging mice was lower than that of the young mice. After 12 wk, EPA+ showed similar muscle mass but increased grip strength compared with EPA−. EPA+ displayed higher insulin sensitivity than EPA−. Immunohistochemistry and gene expression analysis of myosin heavy chains (MyHCs) revealed fast-to-slow fiber type transition in aging muscle, which was partially inhibited by EPA. RNA sequencing (RNA-Seq) analysis suggested that EPA supplementation exerts pathway-specific effects in skeletal muscle including the signatures of slow-to-fast fiber type transition. In conclusion, we revealed that aging skeletal muscle in male mice shows lower grip strength and fiber type changes, both of which can be inhibited by EPA supplementation irrespective of muscle mass alteration.NEW & NOTEWORTHYThis study demonstrated that the early phenotype of skeletal muscle in aging male mice is characterized by muscle weakness with fast-to-slow fiber type transition, which could be ameliorated by feeding with EPA-enriched diet. EPA induced metabolic changes such as an increase in systemic insulin sensitivity and altered muscle transcriptome in the aging mice. These changes may be related to the fiber type transition and influence muscle quality.