{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:57:48Z","timestamp":1779915468772,"version":"3.53.1"},"reference-count":45,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health and Human Performance within the Congdon School of Health Sciences"},{"name":"Congdon School of Health Sciences Summer Undergraduate Research Fellowship (SURF) within the Congdon School of Health Sciences"},{"name":"Shimadzu Partnership for Academics, Research and Quality of Life (SPARQ) Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Muscle loss during sarcopenia and atrophy is also commonly associated with age-related insulin resistance. Interestingly, branched-chain amino acids (BCAA) which are known for stimulating muscle protein synthesis are commonly elevated during insulin resistance and sarcopenic obesity. Objectives: This study investigated the effects of the interplay between atrophy and insulin resistance on insulin sensitivity, mitochondrial metabolism, and BCAA catabolic capacity in a myotube model of skeletal muscle insulin resistance. Methods: C2C12 myotubes were treated with dexamethasone to induce atrophy. Insulin resistance was induced via hyperinsulinemia. Gene and expression were measured using qRT-PCR and Western blot, while mitochondrial and lipid content were assessed using fluorescent staining. Cell metabolism was analyzed via Seahorse metabolic assays. Results: Both dexamethasone-induced atrophy and insulin resistance independently reduced insulin-stimulated pAkt levels, as well as mitochondrial function and content. However, neither treatment affected gene or protein expression associated with mitochondrial biogenesis or content. Although dexamethasone independently reduced insulin sensitivity in otherwise previously insulin-sensitive cells, dexamethasone had no significant effect on extracellular BCAA content. Conclusions: Our findings indicate the metabolic interplay between atrophy and insulin resistance and demonstrate that both can reduce mitochondrial function, though only limited effects were observed on indicators of BCAA catabolism and utilization. This emphasizes the need for future studies to investigate the mechanisms that underlie atrophy and other metabolic disorders to develop new interventions.<\/jats:p>","DOI":"10.3390\/metabo15050322","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T06:40:23Z","timestamp":1747118423000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Effect of Dexamethasone-Mediated Atrophy on Mitochondrial Function and BCAA Metabolism During Insulin Resistance in C2C12 Myotubes"],"prefix":"10.3390","volume":"15","author":[{"given":"Kayla J.","family":"Ragland","sequence":"first","affiliation":[{"name":"Department of Health and Human Performance, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kipton B.","family":"Travis","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmalie R.","family":"Spry","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toheed","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-1440","authenticated-orcid":false,"given":"Pamela M.","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-8807","authenticated-orcid":false,"given":"Roger A.","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13098-023-01022-z","article-title":"Causal relationship between insulin resistance and sarcopenia","volume":"15","author":"Liu","year":"2023","journal-title":"Diabetol. 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