TRB3 regulates skeletal muscle mass in food deprivation-induced atrophy

Ran Hee Choi, Abigail McConahay, João G. Silvestre, Anselmo S. Moriscot, James Carson, Ho Jin Koh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5654-5666
Number of pages13
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2019

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Food Deprivation
Atrophy
Muscle
Skeletal Muscle
Endoplasmic Reticulum Stress
Muscular Atrophy
Muscles
Ubiquitin-Protein Ligases
Skeletal Muscle Fibers
Knockout Mice
Transgenic Mice
Proteolysis
Food
Nutrients
Pharmaceutical Preparations
Tissue
Proteins

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

TRB3 regulates skeletal muscle mass in food deprivation-induced atrophy. / Choi, Ran Hee; McConahay, Abigail; Silvestre, João G.; Moriscot, Anselmo S.; Carson, James; Koh, Ho Jin.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 4, 01.04.2019, p. 5654-5666.

Research output: Contribution to journalArticle

Choi, Ran Hee ; McConahay, Abigail ; Silvestre, João G. ; Moriscot, Anselmo S. ; Carson, James ; Koh, Ho Jin. / TRB3 regulates skeletal muscle mass in food deprivation-induced atrophy. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 4. pp. 5654-5666.
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