{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:41:55Z","timestamp":1790606515650,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,6,16]],"date-time":"2024-06-16T00:00:00Z","timestamp":1718496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022S1A5C2A03092407"],"award-info":[{"award-number":["2022S1A5C2A03092407"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male C57BL6J mice (9\u00a0weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA\u00a0+\u00a0RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using <jats:sup>2<\/jats:sup>H<jats:sub>2<\/jats:sub>O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole\u2010body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic\u2013euglycaemic clamp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EAA\u00a0+\u00a0RET increased muscle mass (10%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and strength (6%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) with concomitant activation of Akt1\/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA\u00a0+\u00a0RET) compared with sedentary groups (10%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), which was associated with increased AchR cluster size and MuSK activation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). EAA\u00a0+\u00a0RET also increased endurance capacity more than RET alone (26%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) by increasing both mitochondrial protein synthesis (53%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and DRP1 activation (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Maximal respiratory capacity increased (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) through activation of the mTORC1\u2010DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1\u2010DRP1 axis activation, ultimately leading to improved basal glucose metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13519","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T06:51:21Z","timestamp":1718607081000},"page":"1651-1663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Free essential amino acid feeding improves endurance during resistance training via DRP1\u2010dependent mitochondrial remodelling"],"prefix":"10.1002","volume":"15","author":[{"given":"Jiwoong","family":"Jang","sequence":"first","affiliation":[{"name":"Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Internal Medicine, Gil Medical Center Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Health Sciences and Technology, GAIHST Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taejeong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Health and Disease, Center for Cardiovascular Research University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanghee","family":"Park","sequence":"additional","affiliation":[{"name":"Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Molecular Medicine, College of Medicine Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee\u2010Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Health Sciences and Technology, GAIHST Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010ho","family":"Koh","sequence":"additional","affiliation":[{"name":"Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Molecular Medicine, College of Medicine Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonil","family":"Cho","sequence":"additional","affiliation":[{"name":"Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Department of Health Sciences and Technology, GAIHST Gachon University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Young","family":"Park","sequence":"additional","affiliation":[{"name":"Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute Gachon University  Incheon Korea"},{"name":"Gachon Biomedical Convergence Institute Gachon University Gil Medical Center  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakthivel","family":"Sadayappan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Health and Disease, Center for Cardiovascular Research University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo\u2010Bum","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Inha University  Incheon Korea"},{"name":"Institute of Sports &amp; Arts Convergence Inha University  Incheon Korea"},{"name":"Department of Biomedical Science, Program in Biomedical Science &amp; Engineering Inha University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. 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