{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:04:30Z","timestamp":1785434670450,"version":"3.56.0"},"reference-count":72,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["536691227"],"award-info":[{"award-number":["536691227"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Skeletal muscle hypertrophy requires a substantial nutrient influx for biomass accretion, but global metabolite exchange during growth is poorly characterized. Therefore, we profiled the metabolite uptake and release in insulin\u2010like growth factor\u20101 (IGF\u20101)\u2010stimulated C2C12 myotubes and human muscle 24\u00a0h after resistance exercise. Differentiated C2C12 myotubes were stimulated to grow with IGF\u20101 (100\u00a0ng\/mL, 24\u00a0h) or received vehicle control. To measure metabolite exchange, we analysed fresh and spent media by gas chromatography\u2013mass spectroscopy metabolomics. In a second experiment, seven untrained adults (three males and four females; age 25.6\u00a0\u00b1\u00a03.2 years; body mass index 23.8\u00a0\u00b1\u00a02.8\u00a0kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) performed single\u2010leg hypertrophy\u2010oriented resistance exercise, with the contralateral leg serving as the control. After 24\u00a0h, we obtained arteriovenous blood samples in the postabsorptive state and analysed plasma by untargeted liquid chromatography\u2013mass spectroscopy metabolomics, characterizing the directionality of metabolite exchange across the human leg. In vitro, IGF\u20101 increased uptake of serine, arginine and pyridoxamine, while enhancing lactate release (all\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05), reflecting anabolic, Warburg\u2010like reprogramming. In vivo, 24\u00a0h postexercise there were modest global shifts (principal components analysis: PC1 8.8%, PC2 6.3% variance) and no significant essential amino acid uptake. Nominal differences (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.05) included increased uptake of peptide\u2010related metabolites (acisoga and 2\u2010amino\u20104\u2010CP) and \u03b1\u2010ketoglutarate, alongside release of C12:0 and C16:0 acylcarnitines. No in vivo differences persisted after false discovery rate correction. Although IGF\u20101 stimulation in vitro promotes coordinated nitrogen\u2010rich metabolite uptake and lactate release, human muscle 24\u00a0h postexercise in a postabsorptive state is characterized by increased peptide turnover and lipid release rather than net amino acid uptake. This indicates limited substrate accumulation and net biomass accretion in the absence of exogenous nutrients.\n                  <\/jats:p>","DOI":"10.1113\/ep094096","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:08:23Z","timestamp":1783055303000},"page":"3784-3799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergent skeletal muscle metabolite exchange in insulin\u2010like growth factor\u20101\u2010stimulated myotubes and resistance\u2010exercised human muscle"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1804-1611","authenticated-orcid":false,"given":"Tim","family":"Havers","sequence":"first","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Department of Fitness &amp; Health IST University of Applied Sciences  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4006-4063","authenticated-orcid":false,"given":"Moritz","family":"Eggelbusch","sequence":"additional","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Meinhold","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"School of Veterinary Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Sing","sequence":"additional","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Okrojek","sequence":"additional","affiliation":[{"name":"Medical Clinic and Polyclinic I Rechts der Isar Hospital of the Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Artati","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Witting","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Core Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Chair of Analytical Food Chemistry, TUM\u2010School of Life Sciences Technical University of Munich  Freising\u2010Weihenstephan Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Lutter","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Obesity, Helmholtz Diabetes Center Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health  Neuherberg Germany"},{"name":"German Center for Diabetes Research  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire V.","family":"Kieker","sequence":"additional","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Starke","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Bioinformatics Technische Universit\u00e4t Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"More","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Bioinformatics Technische Universit\u00e4t Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Hiller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Bioinformatics Technische Universit\u00e4t Braunschweig  Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Dela","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sch\u00f6nfelder","sequence":"additional","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Kafka","sequence":"additional","affiliation":[{"name":"TUM\u2010School of Medicine and Health Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Geisler","sequence":"additional","affiliation":[{"name":"Department of Fitness &amp; 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