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

Henriette Pilegaard; Bengt Saltin; P. Darrell Neufer

doi:10.1113/jphysiol.2002.034850

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

Henriette Pilegaard, Bengt Saltin, P. Darrell Neufer

656 Citations (Scopus)

Abstract

Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) 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-1a 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-1a transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1a 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-1a in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor a, and calcineurin Aa and Aß mRNA were elevated (˜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-1a transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1a may coordinate the activation of metabolic genes in human muscle in response to exercise.

Original language	English
Journal	Journal of Physiology
Volume	546
Issue number	pt. 3
Pages (from-to)	851-858
ISSN	0022-3751
DOIs	https://doi.org/10.1113/jphysiol.2002.034850
Publication status	Published - 2003

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title = "Exercise induces transient transcriptional activation of the PGC-1a gene in human skeletal muscle",

abstract = "Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) 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-1a 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-1a transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1a 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-1a in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor a, and calcineurin Aa and A{\ss} mRNA were elevated (˜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-1a transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1a may coordinate the activation of metabolic genes in human muscle in response to exercise.",

author = "Henriette Pilegaard and Bengt Saltin and Neufer, {P. Darrell}",

note = "PGC-1, metabolic genes, training, transcriptional regulation",

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language = "English",

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TY - JOUR

T1 - Exercise induces transient transcriptional activation of the PGC-1a gene in human skeletal muscle

AU - Pilegaard, Henriette

AU - Saltin, Bengt

AU - Neufer, P. Darrell

N1 - PGC-1, metabolic genes, training, transcriptional regulation

PY - 2003

Y1 - 2003

N2 - Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) 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-1a 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-1a transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1a 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-1a in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor a, and calcineurin Aa and Aß mRNA were elevated (˜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-1a transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1a may coordinate the activation of metabolic genes in human muscle in response to exercise.

AB - Endurance exercise training induces mitochondrial biogenesis in skeletal muscle. The peroxisome proliferator activated receptor co-activator 1a (PGC-1a) 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-1a 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-1a transcription (10- to > 40-fold) and mRNA content (7- to 10-fold), peaking within 2 h after exercise. Activation of PGC-1a 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-1a in cell culture. HKII, mitochondrial transcription factor A, peroxisome proliferator activated receptor a, and calcineurin Aa and Aß mRNA were elevated (˜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-1a transcription and mRNA content in human skeletal muscle. Consistent with its role as a transcriptional coactivator, these findings suggest that PGC-1a may coordinate the activation of metabolic genes in human muscle in response to exercise.

U2 - 10.1113/jphysiol.2002.034850

DO - 10.1113/jphysiol.2002.034850

M3 - Journal article

SN - 0022-3751

VL - 546

SP - 851

EP - 858

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - pt. 3

ER -

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

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