Popov Daniil V, Lysenko Evgeny A, Butkov Alexey D, Vepkhvadze Tatiana F, Perfilov Dmitriy V, Vinogradova Olga L
Laboratory of Exercise Physiology, Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
Faculty of Fundamental Medicine, M. V. Lomonosov Moscow State University, Moscow, Russia.
Exp Physiol. 2017 Mar 1;102(3):366-375. doi: 10.1113/EP086074. Epub 2017 Feb 9.
What is the central question of this study? This study was designed to investigate the role of AMPK in the regulation of PGC-1α gene expression via the alternative promoter through a cAMP response element-binding protein-1-dependent mechanism in human skeletal muscle. What is the main finding and its importance? Low-intensity exercise markedly increased the expression of PGC-1α mRNA via the alternative promoter, without increases in ACC (a marker of AMPK activation) and AMPK phosphorylation. A single dose of the AMPK activator metformin indicated that AMPK was not involved in regulating PGC-1α mRNA expression via the alternative promoter in endurance-trained human skeletal muscle. In human skeletal muscle, PGC-1α is constitutively expressed via the canonical promoter. In contrast, the expression of PGC-1α mRNA via the alternative promoter was found to be highly dependent on the intensity of exercise and to contribute largely to the postexercise increase of total PGC-1α mRNA. This study investigated the role of AMPK in regulating PGC-1α gene expression via the alternative promoter through a cAMP response element-binding protein-1-dependent mechanism in human skeletal muscle. AMPK activation and PGC-1α gene expression were assayed in skeletal muscle of nine endurance-trained men before and after low-intensity exercise (38% of maximal oxygen uptake) and with or without administration of a single dose (2 g) of the AMPK activator metformin. Low-intensity exercise markedly and significantly increased (∼100-fold, P < 0.05) the expression of PGC-1α mRNA via the alternative promoter, without increasing ACC (a marker of AMPK activation) and AMPK phosphorylation. Moreover, in contrast to placebo, metformin increased the level of ACC phosphorylation immediately after exercise (2.6-fold, P < 0.05). However postexercise expression of PGC-1α gene via the alternative promoter was not affected. This study was unable to confirm that AMPK plays a role in regulating PGC-1α gene expression via the alternative promoter in endurance-trained human skeletal muscle.
本研究的核心问题是什么？本研究旨在通过一种依赖于环磷酸腺苷反应元件结合蛋白-1的机制，研究腺苷酸活化蛋白激酶（AMPK）在通过可变启动子调节人骨骼肌中过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）基因表达中的作用。主要发现及其重要性是什么？低强度运动通过可变启动子显著增加了PGC-1α mRNA的表达，而乙酰辅酶A羧化酶（ACC，AMPK激活的标志物）和AMPK磷酸化水平并未增加。单剂量的AMPK激活剂二甲双胍表明，在耐力训练的人骨骼肌中，AMPK不参与通过可变启动子调节PGC-1α mRNA的表达。在人骨骼肌中，PGC-1α通过经典启动子组成性表达。相比之下，发现通过可变启动子的PGC-1α mRNA表达高度依赖于运动强度，并在很大程度上促成了运动后总PGC-1α mRNA的增加。本研究通过一种依赖于环磷酸腺苷反应元件结合蛋白-1的机制，研究了AMPK在通过可变启动子调节人骨骼肌中PGC-1α基因表达中的作用。在9名耐力训练男性的骨骼肌中，在低强度运动（最大摄氧量的38%）前后以及给予或不给予单剂量（2 g）的AMPK激活剂二甲双胍的情况下，检测了AMPK激活和PGC-1α基因表达。低强度运动通过可变启动子显著且明显地增加了（约100倍，P<0.05）PGC-1α mRNA的表达，而未增加ACC（AMPK激活的标志物）和AMPK磷酸化水平。此外，与安慰剂相比，二甲双胍在运动后立即增加了ACC磷酸化水平（2.6倍，P<0.05）。然而，运动后通过可变启动子的PGC-1α基因表达未受影响。本研究无法证实AMPK在耐力训练的人骨骼肌中通过可变启动子调节PGC-1α基因表达中起作用。
