{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T06:02:24Z","timestamp":1774159344684,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000990","name":"Australian Catholic University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000990","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Health and Medical Research Council of Australia","award":["1085460"],"award-info":[{"award-number":["1085460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Acute exercise remodels many interconnected biochemical pathways in metabolically active tissues. This remodeling involves the activation of the energy-sensing AMP-activated protein kinase (AMPK) to maintain cellular energy homeostasis. Critical energy reserves of glycogen, primarily stored in liver and skeletal muscle and known to interact with AMPK, are utilized to help meet increased energy demands with exercise. However, the breadth of metabolic pathways regulated by acute exercise and AMPK\u2019s interactive roles with glycogen remain incompletely understood. This study therefore aimed to map mouse liver and skeletal muscle metabolite responses to continuous acute exercise and disruption of AMPK-glycogen interactions. Methods: Liquid chromatography\u2013mass spectrometry-based untargeted metabolomics was used to measure the relative abundance of liver and gastrocnemius muscle metabolites at rest and following an acute bout of continuous treadmill running in wild type (WT) and AMPK transgenic mice with double knock-in (DKI) mutations in the \u03b2 subunit carbohydrate binding module that mediates glycogen binding. Results: Over 200 total metabolites were identified\/annotated across liver and skeletal muscle, including 45 metabolites responsive to exercise (p &lt; 0.05; FDR &lt; 0.1). Exercise-regulated metabolites included known metabolic pathways and metabolites never associated or with only emerging evidence related to exercise (e.g., ergothioneine) and\/or AMPK-glycogen interactions (N6,N6,N6-trimethyl-L-lysine, a precursor of L-carnitine). Conclusions: Liver and skeletal muscle metabolomic profiles displayed shifts between WT and DKI mice at rest, with shifts also detected following a continuous acute exercise bout. An interaction effect was also observed in skeletal muscle, suggesting differential muscle metabolite responses to acute exercise in DKI mice that may contribute to their functional impairments in metabolic control and exercise capacity versus WT. Collectively, these findings expand the molecular landscape of acute exercise and reveal liver and muscle metabolites underlying exercise-induced metabolic responses.<\/jats:p>","DOI":"10.3390\/metabo16030205","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:49:58Z","timestamp":1774003798000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Remodeling of the Mouse Liver and Skeletal Muscle Metabolome in Response to Continuous Acute Exercise and Disruption of AMPK-Glycogen Interactions"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-6236","authenticated-orcid":false,"given":"Mehdi R.","family":"Belhaj","sequence":"first","affiliation":[{"name":"Centre for Human Metabolism and Performance, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0775-9581","authenticated-orcid":false,"given":"David I.","family":"Broadhurst","sequence":"additional","affiliation":[{"name":"School of Science, Edith Cowan University, Joondalup, WA 6027,  Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dignan","sequence":"additional","affiliation":[{"name":"School of Science, Edith Cowan University, Joondalup, WA 6027,  Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-8872","authenticated-orcid":false,"given":"Jamie","family":"Whitfield","sequence":"additional","affiliation":[{"name":"Centre for Human Metabolism and Performance, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Murray-Segal","sequence":"additional","affiliation":[{"name":"Metabolic Signalling Laboratory, St. Vincent\u2019s Institute of Medical Research, Fitzroy, VIC 3065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6240-4092","authenticated-orcid":false,"given":"Naomi X. Y.","family":"Ling","sequence":"additional","affiliation":[{"name":"Metabolic Signalling Laboratory, St. Vincent\u2019s Institute of Medical Research, Fitzroy, VIC 3065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-1440","authenticated-orcid":false,"given":"Jonathan S.","family":"Oakhill","sequence":"additional","affiliation":[{"name":"Metabolic Signalling Laboratory, St. Vincent\u2019s Institute of Medical Research, Fitzroy, VIC 3065, Australia"},{"name":"Department of Medicine, University of Melbourne, Parkville, VIC  3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce E.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Centre for Human Metabolism and Performance, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3002, Australia"},{"name":"Department of Medicine, University of Melbourne, Parkville, VIC  3052, Australia"},{"name":"Protein Chemistry and Metabolism, St. Vincent\u2019s Institute of Medical Research, Fitzroy, VIC 3065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Hawley","sequence":"additional","affiliation":[{"name":"Centre for Human Metabolism and Performance, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3002, Australia"},{"name":"Department of Sport and Exercise Sciences, Institute of Sport,  Manchester Metropolitan University, Manchester M1 7EL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey N.","family":"Reinke","sequence":"additional","affiliation":[{"name":"School of Science, Edith Cowan University, Joondalup, WA 6027,  Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-7082","authenticated-orcid":false,"given":"Nolan J.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Centre for Human Metabolism and Performance, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1152\/jappl.1993.75.2.712","article-title":"Human muscle metabolism during intermittent maximal exercise","volume":"75","author":"Gaitanos","year":"1993","journal-title":"J. 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