Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle

J Physiol. 2003 Feb 1;546(Pt 3):851-8. doi: 10.1113/jphysiol.2002.034850.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • Adult
  • Bicycling
  • Calcineurin / genetics
  • Citrate (si)-Synthase / genetics
  • Citrate (si)-Synthase / metabolism
  • DNA-Binding Proteins / genetics
  • Exercise / physiology*
  • Gene Expression Regulation / physiology*
  • Hexokinase / genetics
  • Humans
  • Mitochondrial Proteins*
  • Muscle, Skeletal / physiology*
  • NF-E2-Related Factor 1
  • Nuclear Proteins / genetics
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • Physical Education and Training
  • RNA, Messenger / metabolism
  • Time Factors
  • Trans-Activators / genetics
  • Transcription Factors / genetics*
  • Transcription, Genetic / physiology*


  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • NF-E2-Related Factor 1
  • NRF1 protein, human
  • Nuclear Proteins
  • Nuclear Respiratory Factor 1
  • Nuclear Respiratory Factors
  • RNA, Messenger
  • TFAM protein, human
  • Trans-Activators
  • Transcription Factors
  • mitochondrial transcription factor A
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Citrate (si)-Synthase
  • Hexokinase
  • Calcineurin