Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle.
Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1alpha (PGC-1alpha) has recently been identified as a nuclear factor critical for coordinating the activation of genes required for mitochondrial biogenesis in cell culture and rodent skeletal muscle. To determine whether PGC-1alpha transcription is regulated by acute exercise and exercise training in human skeletal muscle, seven male subjects performed 4 weeks of one-legged knee extensor exercise training. At the end of training, subjects completed 3 h of two-legged knee extensor exercise. Biopsies were obtained from the vastus lateralis muscle of both the untrained and trained legs before exercise and after 0, 2, 6 and 24 h of recovery. Time to exhaustion (2 min maximum resistance), as well as hexokinase II (HKII), citrate synthase and 3-hydroxyacyl-CoA dehydrogenase mRNA, were higher in the trained than the untrained leg prior to exercise. Exercise induced a marked transient increase (P < 0.05) in PGC-1alpha transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1alpha was greater in the trained leg despite the lower relative workload. Interestingly, exercise did not affect nuclear respiratory factor 1 (NRF-1) mRNA, a gene induced by PGC-1alpha in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor alpha, and calcineurin Aalpha and Abeta mRNA were elevated (approximately 2- to 6-fold; P < 0.05) at 6 h of recovery in the untrained leg but did not change in the trained leg. The present data demonstrate that exercise induces a dramatic transient increase in PGC-1alpha transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1alpha may coordinate the activation of metabolic genes in human muscle in response to exercise.
Pilegaard
Henriette
H
Copenhagen Muscle Research Centre and The August Krogh Institute, University of Copenhagen, Denmark.
Saltin
Bengt
B
Neufer
P Darrell
PD
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000328:Adult; D001642:Bicycling; D019703:Calcineurin / Q000235:genetics; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006593:Hexokinase / Q000235:genetics; D006801:Humans; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology*; D051265:NF-E2-Related Factor 1; D009687:Nuclear Proteins / Q000235:genetics; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D010806:Physical Education and Training; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; C495633:NRF1 protein, human; D009687:Nuclear Proteins; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D012333:RNA, Messenger; C499631:TFAM protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D006593:Hexokinase; D019703:Calcineurin