AMPK does not play a requisite role in regulation of PPARGC1A gene expression via the alternative promoter in endurance‐trained human skeletal muscle

• Published in: Experimental physiology 2017-03, Vol.102 (3), p.366-375
• Main Authors: Popov, Daniil V., Lysenko, Evgeny A., Butkov, Alexey D., Vepkhvadze, Tatiana F., Perfilov, Dmitriy V., Vinogradova, Olga L.
• Format: Article
• Language: English
• Subjects: Adult; alternative promoter; Amino Acid Sequence; AMP-Activated Protein Kinases - metabolism; Base Sequence; exercise; Exercise - physiology; Gene Expression - genetics; Humans; Male; metformin; Muscle, Skeletal - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; PGC‐1alpha; Phosphorylation - genetics; Physical Endurance - genetics; Physical Endurance - physiology; Promoter Regions, Genetic - genetics; RNA, Messenger - metabolism; skeletal muscle; Young Adult
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/EP086074

New Findings 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 ACCSer79/222 (a marker of AMPK activation) and AMPKThr172 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