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Creb coactivators direct anabolic responses and enhance performance of skeletal muscle

Academic Article
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Overview

authors

  • Bruno, N. E.
  • Kelly, K. A.
  • Hawkins, R.
  • Bramah-Lawani, M.
  • Amelio, A. L.
  • Nwachukwu, J. C.
  • Nettles, Kendall
  • Conkright, Michael

publication date

  • May 2014

journal

  • EMBO Journal  Journal

abstract

  • During the stress response to intense exercise, the sympathetic nervous system (SNS) induces rapid catabolism of energy reserves through the release of catecholamines and subsequent activation of protein kinase A (PKA). Paradoxically, chronic administration of sympathomimetic drugs (β-agonists) leads to anabolic adaptations in skeletal muscle, suggesting that sympathetic outflow also regulates myofiber remodeling. Here, we show that β-agonists or catecholamines released during intense exercise induce Creb-mediated transcriptional programs through activation of its obligate coactivators Crtc2 and Crtc3. In contrast to the catabolic activity normally associated with SNS function, activation of the Crtc/Creb transcriptional complex by conditional overexpression of Crtc2 in the skeletal muscle of transgenic mice fostered an anabolic state of energy and protein balance. Crtc2-overexpressing mice have increased myofiber cross-sectional area, greater intramuscular triglycerides and glycogen content. Moreover, maximal exercise capacity was enhanced after induction of Crtc2 expression in transgenic mice. Collectively these findings demonstrate that the SNS-adrenergic signaling cascade coordinates a transient catabolic stress response during high-intensity exercise, which is followed by transcriptional reprogramming that directs anabolic changes for recovery and that augments subsequent exercise performance.

subject areas

  • Animals
  • Animals, Newborn
  • Catecholamines
  • Cells, Cultured
  • Exercise Tolerance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle, Skeletal
  • Physical Conditioning, Animal
  • Sympathetic Nervous System
  • Transcription Factors
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Research

keywords

  • Creb-regulated transcriptional coregulators
  • cAMP-response element-binding protein
  • hypertrophy
  • skeletal muscle
  • sympathetic nervous system
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Identity

PubMed Central ID

  • PMC4193935

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1002/embj.201386145

PubMed ID

  • 24674967
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Additional Document Info

start page

  • 1027

end page

  • 1043

volume

  • 33

issue

  • 9

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