{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T14:55:52Z","timestamp":1774968952244,"version":"3.50.1"},"posted":{"date-parts":[[2025,7,19]]},"group-title":"Physiology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,19]]},"abstract":"<jats:title>\n                  <jats:bold>ABSTRACT<\/jats:bold>\n                <\/jats:title>\n                <jats:p>\n                  Tribbles 3 (TRB3) is a pseudokinase and its expression has been shown to disrupt glucose metabolism through the inhibition of Akt under obese and diabetic conditions. We recently found that overexpression of TRB3 in mouse skeletal muscle decreased skeletal muscle mass and function, leading to muscle atrophy. Here, we examined whether TRB3 affects exercise training-induced skeletal muscle adaptation. We trained muscle-specific TRB3 transgenic (TG) and wild-type (WT) littermates using a voluntary wheel running protocol for 6 weeks and found that TG mice ran significantly less weekly distances than WT littermates. To exclude the possibility that different skeletal muscle adaptations would be produced due to different training intensities, involuntary treadmill exercise (TM) was used as a training regimen. At the 5\n                  <jats:sup>th<\/jats:sup>\n                  week of training, we measured glucose tolerance and found that trained TG mice showed glucose intolerance compared to WT littermates. Furthermore, overexpression of TRB3 significantly suppressed the expression of genes needed for glucose uptake and mitochondrial biogenesis, independent of training status. To further determine the role of TRB3 in exercise-induced adaptation, TRB3 knockout (KO) mice were trained by voluntary and involuntary exercise protocols. KO mice presented improved glucose tolerance compared to WT littermates independent of training status. However, we did not observe significant change in the expression of markers for glucose uptake and mitochondrial biogenesis. Taken together, our results indicate that TRB3 in skeletal muscle blunts the benefits of exercise-induced skeletal muscle adaptation.\n                <\/jats:p>","DOI":"10.1101\/2025.07.16.665065","type":"posted-content","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T05:50:11Z","timestamp":1752990611000},"source":"Crossref","is-referenced-by-count":1,"title":["Tribbles 3 blunts exercise-induced skeletal muscle adaptation"],"prefix":"10.64898","author":[{"given":"Ran Hee","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"McConahay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie B.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"Ojemuyiwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooklyn J.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ha-Won","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-0938","authenticated-orcid":false,"given":"Ho-Jin","family":"Koh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025072301450807000_2025.07.16.665065v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00027.2014"},{"key":"2025072301450807000_2025.07.16.665065v1.2","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/ejcn.2017.53","article-title":"Novel approaches for the promotion of physical activity and exercise for prevention and management of type 2 diabetes","volume":"71","year":"2017","journal-title":"Eur J Clin Nutr"},{"key":"2025072301450807000_2025.07.16.665065v1.3","doi-asserted-by":"crossref","unstructured":"Baar K , Wende AR , Jones TE , Marison M , Nolte LA , Chen M , Kelly DP , and Holloszy JO. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 16: 1879-1886, 2002.","DOI":"10.1096\/fj.02-0367com"},{"key":"2025072301450807000_2025.07.16.665065v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2006.07.003"},{"key":"2025072301450807000_2025.07.16.665065v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810339105"},{"key":"2025072301450807000_2025.07.16.665065v1.6","doi-asserted-by":"crossref","unstructured":"Choi RH , McConahay A , Jeong HW , McClellan JL , Hardee JP , Carson JA , Hirshman MF , Goodyear LJ , and Koh HJ. Tribbles 3 regulates protein turnover in mouse skeletal muscle. Biochem Biophys Res Commun 493: 1236-1242, 2017.","DOI":"10.1016\/j.bbrc.2017.09.134"},{"key":"2025072301450807000_2025.07.16.665065v1.7","doi-asserted-by":"crossref","unstructured":"Choi RH , McConahay A , Silvestre JG , Moriscot AS , Carson JA , and Koh HJ. TRB3 regulates skeletal muscle mass in food deprivation-induced atrophy. FASEB J: fj201802145RR, 2019.","DOI":"10.1096\/fj.201802145RR"},{"key":"2025072301450807000_2025.07.16.665065v1.8","doi-asserted-by":"publisher","DOI":"10.1053\/meta.2001.22568"},{"key":"2025072301450807000_2025.07.16.665065v1.9","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302"},{"key":"2025072301450807000_2025.07.16.665065v1.10","doi-asserted-by":"crossref","unstructured":"Dela F , Mikines KJ , von Linstow M , Secher NH , and Galbo H. Effect of training on insulin-mediated glucose uptake in human muscle. Am J Physiol 263: E1134-1143, 2006.","DOI":"10.1152\/ajpendo.2006.263.6.E1134"},{"key":"2025072301450807000_2025.07.16.665065v1.11","doi-asserted-by":"crossref","unstructured":"Derave W , Lund S , Holman GD , Wojtaszewski J , Pedersen O , and Richter EA. Contraction-stimulated muscle glucose transport and GLUT-4 surface content are dependent on glycogen content. 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