Mouse Cachectic Skeletal Muscle mTORC1 Signaling in Response to Acute Eccentric Contractions Academic Article uri icon

abstract

  • Eccentric contraction (EC) induced skeletal muscle hypertrophy involves the activation of protein synthesis through mTORC1 signaling. Cancer cachexia disruption of muscle protein turnover regulation is well established, but whether increased use regulates suppressed muscle protein synthesis warrants further investigation. We recently demonstrated severely cachectic muscle can initiate a growth response to repeated ECs. However, the EC activation of mTORC1 signaling in cachectic muscle has not been investigated. The purpose of this study was to determine if mTORC1 signaling and protein synthesis in cachectic muscle from 2 distinct preclinical cancer cachexia models could respond to EC. Male, ApcMin/+ (N=5; 15% body weight loss) and Lewis Lung Carcinoma (LLC) tumorbearing (N=8; 14% body weight loss) mice performed 1 bout (10 sets of 6 repetitions) of EC and were sacrificed 3h postcontraction. The left TA performed EC while the right TA served as intraanimal control. C57BL/6 (WT) mice served as controls. In control muscle ApcMin/+ and LLC mice had decreased muscle mass, p70S6K(T389) phosphorylation, and protein synthesis compared to WT controls. Cachexia did not inhibit the acute ECinduction of p70S6K(T389) phosphorylation in ApcMin/+ or LLC mice. While EC induced protein synthesis in ApcMin/+ mice, protein synthesis remained suppressed compared to WT mice. Interestingly, EC did not stimulate muscle protein synthesis in LLC mice. Although cachexia suppressed muscle anabolic signaling, cachectic muscle maintains the ability to activate mTORC1 signaling by EC. However, in LLCinduced cachexia there is a disconnect between mTORC1 activation and the induction of protein synthesis. Further studies are required to determine the tumor specific effects that regulate the anabolic response to eccentric contractions in cachectic muscle.Support or Funding InformationSupported by NIH/NCI R01CA121249

published proceedings

  • The FASEB Journal

author list (cited authors)

  • Hardee, J. P., Gao, S., VanderVeen, B. N., Fix, D. K., Hetzler, K. L., & Carson, J. A.

complete list of authors

  • Hardee, Justin P||Gao, Song||VanderVeen, Brandon N||Fix, Dennis K||Hetzler, Kimbell L||Carson, James A

publisher