Effect of Sirt6 deficiency on transcriptome in skeletal muscle of mice

Expanding the exercise capacity is an emerging strategy to combat metabolic diseases. Skeletal muscle fiber type determination is critical for the exercise performance, but the regulatory basis is largely unknown. Here, we report that Sirt6 has a role in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. To elucidate molecular mechanisms, we performed RNA-sequencing analysis using WT and skeletal muscle-specific Sirt6 KO mice. Transcriptomic analysis enabled us to discover major signaling nodes altered by Sirt6 deficiency in close association with mitochondrial function and muscle phenotypes.提升运动能力是对抗代谢疾病的新兴策略。骨骼肌肌纤维分型对运动表现至关重要，但其调控机制目前仍未完全明确。本研究证实，沉默信息调节因子6（Sirt6）可调控肌纤维向氧化型转化，且Sirt6激活剂可作为运动模拟剂。为阐明其分子机制，本研究利用野生型（WT）及骨骼肌特异性Sirt6敲除（KO）小鼠开展了RNA测序（RNA-sequencing）分析。通过转录组分析，本研究发现Sirt6缺失所改变的核心信号节点，与线粒体功能及肌肉表型密切相关。