1. Creb coactivators direct anabolic responses and enhance performance of skeletal muscle.
- Author
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Bruno, Nelson E, Kelly, Kimberly A, Hawkins, Richard, Bramah‐Lawani, Mariam, Amelio, Antonio L, Nwachukwu, Jerome C, Nettles, Kendall W, and Conkright, Michael D
- Subjects
SKELETAL muscle ,PERFORMANCE evaluation ,ADRENERGIC receptors ,CREB protein ,SYMPATHETIC nervous system ,CYCLIC-AMP-dependent protein kinase - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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