Department of Biology, Centre of Inflammation and Metabolism, Copenhagen Muscle Research Centre, University of Copenhagen, August Krogh Building, Universitetsparken 13, 2100, Copenhagen Ø, Denmark.
Pflugers Arch. 2010 Jun;460(1):153-62. doi: 10.1007/s00424-010-0834-0. Epub 2010 Apr 19.
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1alpha-mediated effects in skeletal muscle. In addition, regulation of PGC-1alpha expression and activity in skeletal muscle is described. The impact of changes in PGC-1alpha expression in mouse skeletal muscle and the ability of PGC-1alpha to regulate multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.
生活方式相关疾病的发病率正在迅速上升，至少部分原因是体力活动减少。有规律的体力活动对健康的有益影响包括骨骼肌的代谢适应，据认为这是由每次单一运动对瞬时基因反应的累积效应引起的，但这是如何调节的呢？转录共激活因子过氧化物酶体增殖物激活受体-γ共激活因子（PGC）-1α是一个潜在的候选者，它已被确定为线粒体生物发生的主要调节因子，但也被证明可以调节血管生成和抗氧化防御中涉及的蛋白质，以及影响炎症标志物的表达。运动通过翻译后修饰增加 PGC-1α 的转录和潜在的 PGC-1α 活性，并且当运动重复时，同时的 PGC-1α 介导的基因调节被认为是骨骼肌适应的潜在机制。目前的综述介绍了 PGC-1α 在基础状态和运动训练应答中调节骨骼肌代谢相关、抗氧化和炎症蛋白的一些关键发现，并描述了 PGC-1α 在骨骼肌中的介导作用的功能意义。此外，还描述了骨骼肌中 PGC-1α 表达和活性的调节。PGC-1α 在小鼠骨骼肌中的表达变化以及 PGC-1α 调节多种途径和功能的能力强调了 PGC-1α 在人类骨骼肌适应中的潜在重要性。在不活动的生活方式中缺乏运动诱导的 PGC-1α 介导的基因调节，被认为会导致骨骼肌氧化能力降低和代谢功能受损。
