Loss of REDD1 augments the rate of the overload-induced increase in muscle mass

Bradley S. Gordon, Chang Liu, Jennifer L. Steiner, Gustavo A. Nader, Leonard S. Jefferson, Scot R. Kimball

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The overload-induced increase in muscle mass is accompanied by protein accretion; however, the initiating events are poorly understood. Regulated in Development and DNA Damage 1 (REDD1), a repressor of the mechanistic target of rapamycin in complex 1 (mTORC1), blunts the elevation in protein synthesis induced by acute muscle contractions. Therefore, this study was designed to determine whether REDD1 alters the rate of the overload-induced increase in muscle mass. Wild-type (WT) and REDD1-null mice underwent unilateral functional overload (OV) of the plantaris, while the contralateral sham leg served as a control. After 3 and 5 days of OV, puromycin incorporation was used as a measurement of protein synthesis. The percent increase in plantaris wet weight and protein content was greater in REDD1-null mice after 3, 5, and 10 days OV. The overload-stimulated rate of protein synthesis in the plantaris was similar between genotypes after 3 days OV, but translational capacity was lower in REDD1-null mice, indicating elevated translational efficiency. This was likely due to elevated absolute mTORC1 signaling [phosphorylation of p70S6K1 (Thr-389) and 4E-BP1 (Ser-65)]. By 5 days of OV, the rate of protein synthesis in REDD1-null mice was lower than WT mice with no difference in absolute mTORC1 signaling. Additionally, markers of autophagy (LC3II/I ratio and p62 protein) were decreased to a greater absolute extent after 3 days OV in REDD1-null mice. These data suggest that loss of REDD1 augments the rate of the OV-induced increase in muscle mass by altering multiple protein balance pathways.

Original languageEnglish (US)
Pages (from-to)R545-R557
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume311
Issue number3
DOIs
StatePublished - 2016

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Loss of REDD1 augments the rate of the overload-induced increase in muscle mass'. Together they form a unique fingerprint.

Cite this