title: AMPK does not play a requisite role in regulation of PPARGC1A gene expression via the alternative promoter in endurance-trained human skeletal muscle.
abstract: 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 AMPKThr172phosphorylation. 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 ACCSer79/222(a marker of AMPK activation) and AMPKThr172phosphorylation. Moreover, in contrast to placebo, metformin increased the level of ACCSer79/222phosphorylation 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.
authors.affiliation: 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.
authors.forename: Daniil V
authors.identifier: 0000-0002-3981-244X
authors.initials: DV
authors.lastname: Popov
authors.affiliation: 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.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Lysenko
authors.affiliation: Laboratory of Exercise Physiology, Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexey D
authors.initials: AD
authors.lastname: Butkov
authors.affiliation: Laboratory of Exercise Physiology, Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: Tatiana F
authors.initials: TF
authors.lastname: Vepkhvadze
authors.affiliation: Laboratory of Exercise Physiology, Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: Dmitriy V
authors.initials: DV
authors.lastname: Perfilov
authors.affiliation: 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.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Vinogradova
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015444:Exercise / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D010807:Physical Endurance / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases
keywords: PGC-1alpha; alternative promoter; exercise; metformin; skeletal muscle