TRB3 regulates skeletal muscle mass in food deprivation–induced atrophy

The FASEB JournalVolume 33, Issue 4 p. 5654-5666 ResearchFree to Read TRB3 regulates skeletal muscle mass in food deprivation–induced atrophy Ran Hee Choi, Ran Hee Choi Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorAbigail McConahay, Abigail McConahay Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorJoão G. Silvestre, João G. Silvestre Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USA Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorAnselmo S. Moriscot, Anselmo S. Moriscot Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorJames A. Carson, James A. Carson Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorHo-Jin Koh, Corresponding Author Ho-Jin Koh kohh@mailbox.sc.edu Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USA Correspondence: Department of Exercise Science, Arnold School of Public Health, University of South Carolina, 921 Assembly St., Columbia, SC 29208, USA. E-mail: kohh@mailbox.sc.eduSearch for more papers by this author Ran Hee Choi, Ran Hee Choi Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorAbigail McConahay, Abigail McConahay Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorJoão G. Silvestre, João G. Silvestre Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USA Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorAnselmo S. Moriscot, Anselmo S. Moriscot Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorJames A. Carson, James A. Carson Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USASearch for more papers by this authorHo-Jin Koh, Corresponding Author Ho-Jin Koh kohh@mailbox.sc.edu Division of Applied Physiology, Department of Exercise Science, University of South Carolina, Columbia, South Carolina, USA Correspondence: Department of Exercise Science, Arnold School of Public Health, University of South Carolina, 921 Assembly St., Columbia, SC 29208, USA. E-mail: kohh@mailbox.sc.eduSearch for more papers by this author First published: 25 January 2019 https://doi.org/10.1096/fj.201802145RRCitations: 5 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat ABSTRACT Tribbles 3 (TRB3) is a pseudokinase that has been found in multiple tissues in response to various stress stimuli, such as nutrient deprivation and endoplasmic reticulum (ER) stress. We recently found that TRB3 has the potential to regulate skeletal muscle mass at the basal state. However, it has not yet been explored whether TRB3 regulates skeletal muscle mass under atrophic conditions. Here, we report that food deprivation for 48 h in mice significantly reduces muscle mass by ∼15% and increases TRB3 expression, which is associated with increased ER stress. Interestingly, inhibition of ER stress in C2C12 myotubes reduces food deprivation–induced expression of TRB3 and muscle-specific E3-ubiquitin ligases. In further in vivo experiments, muscle-specific TRB3 transgenic mice increase food deprivation–induced muscle atrophy compared with wild-type (WT) littermates presumably by the increased proteolysis. On the other hand, TRB3 knockout mice ameliorate food deprivation–induced atrophy compared with WT littermates by preserving a higher protein synthesis rate. These results indicate that TRB3 plays a pivotal role in skeletal muscle mass regulation under food deprivation–induced muscle atrophy and TRB3 could be a pharmaceutical target to prevent skeletal muscle atrophy.—Choi, R. H., McConahay, A., Silvestre, J. G., Moriscot, A. S., Carson, J. A., Koh, H.-J. TRB3 regulates skeletal muscle mass in food deprivation–induced atrophy. FASEB J. 33, 5654–5666 (2019). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2fj201802145rr-sup-0549.pdfPDF document, 728.7 KB Supplementary Material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume33, Issue4April 2019Pages 5654-5666 RelatedInformation