Selective activation of AMPK-PGC-1a or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation.

P. J. Atherton, J. Babraj, K. Smith, J. Singh, M. J. Rennie, Henning Wackerhage

Research output: Contribution to journalArticle

299 Citations (Scopus)

Abstract

Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximate to 2-fold and increased PGC-1 alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3 beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1 alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.

Original languageEnglish
Pages (from-to)786-788
Number of pages2
JournalThe FASEB Journal
Volume19
DOIs
Publication statusPublished - May 2005

Keywords

  • PKB(Akt)
  • signal transduction
  • skeletal muscle
  • PROTEIN-KINASE-B
  • RAT SKELETAL-MUSCLE
  • GLYCOGEN-SYNTHASE KINASE-3
  • MAMMALIAN TARGET
  • MITOCHONDRIAL BIOGENESIS
  • FIBER-TYPE
  • ELONGATION-FACTOR-2 KINASE
  • PHOSPHORYLATION SITE
  • MYOTUBE HYPERTROPHY
  • COACTIVATOR PGC-1

Cite this

Selective activation of AMPK-PGC-1a or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. / Atherton, P. J.; Babraj, J.; Smith, K.; Singh, J.; Rennie, M. J.; Wackerhage, Henning.

In: The FASEB Journal, Vol. 19, 05.2005, p. 786-788.

Research output: Contribution to journalArticle

Atherton, P. J. ; Babraj, J. ; Smith, K. ; Singh, J. ; Rennie, M. J. ; Wackerhage, Henning. / Selective activation of AMPK-PGC-1a or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation. In: The FASEB Journal. 2005 ; Vol. 19. pp. 786-788.
@article{d957ae203dd14d25917ea63e7d4520b4,
title = "Selective activation of AMPK-PGC-1a or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation.",
abstract = "Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximate to 2-fold and increased PGC-1 alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3 beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1 alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the {"}AMPK-PKB switch.{"} We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.",
keywords = "PKB(Akt), signal transduction, skeletal muscle, PROTEIN-KINASE-B, RAT SKELETAL-MUSCLE, GLYCOGEN-SYNTHASE KINASE-3, MAMMALIAN TARGET, MITOCHONDRIAL BIOGENESIS, FIBER-TYPE, ELONGATION-FACTOR-2 KINASE, PHOSPHORYLATION SITE, MYOTUBE HYPERTROPHY, COACTIVATOR PGC-1",
author = "Atherton, {P. J.} and J. Babraj and K. Smith and J. Singh and Rennie, {M. J.} and Henning Wackerhage",
year = "2005",
month = "5",
doi = "10.1096/FJ.04-2179FJE",
language = "English",
volume = "19",
pages = "786--788",
journal = "The FASEB Journal",
issn = "0892-6638",
publisher = "FEDERATION AMER SOC EXP BIOL",

}

TY - JOUR

T1 - Selective activation of AMPK-PGC-1a or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation.

AU - Atherton, P. J.

AU - Babraj, J.

AU - Smith, K.

AU - Singh, J.

AU - Rennie, M. J.

AU - Wackerhage, Henning

PY - 2005/5

Y1 - 2005/5

N2 - Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximate to 2-fold and increased PGC-1 alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3 beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1 alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.

AB - Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximate to 2-fold and increased PGC-1 alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3 beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1 alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.

KW - PKB(Akt)

KW - signal transduction

KW - skeletal muscle

KW - PROTEIN-KINASE-B

KW - RAT SKELETAL-MUSCLE

KW - GLYCOGEN-SYNTHASE KINASE-3

KW - MAMMALIAN TARGET

KW - MITOCHONDRIAL BIOGENESIS

KW - FIBER-TYPE

KW - ELONGATION-FACTOR-2 KINASE

KW - PHOSPHORYLATION SITE

KW - MYOTUBE HYPERTROPHY

KW - COACTIVATOR PGC-1

U2 - 10.1096/FJ.04-2179FJE

DO - 10.1096/FJ.04-2179FJE

M3 - Article

VL - 19

SP - 786

EP - 788

JO - The FASEB Journal

JF - The FASEB Journal

SN - 0892-6638

ER -