| First Author | Bruno NE | Year | 2014 |
| Journal | EMBO J | Volume | 33 |
| Issue | 9 | Pages | 1027-43 |
| PubMed ID | 24674967 | Mgi Jnum | J:210968 |
| Mgi Id | MGI:5572980 | Doi | 10.1002/embj.201386145 |
| Citation | Bruno NE, et al. (2014) Creb coactivators direct anabolic responses and enhance performance of skeletal muscle. EMBO J 33(9):1027-43 |
| abstractText | 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 (beta-agonists) leads to anabolic adaptations in skeletal muscle, suggesting that sympathetic outflow also regulates myofiber remodeling. Here, we show that beta-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. |
