{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:29:17Z","timestamp":1781184557436,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20F20111"],"award-info":[{"award-number":["20F20111"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K10910"],"award-info":[{"award-number":["23K10910"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ketone body supplementation has gained attention for its metabolic effects, but its impact on exercise metabolism remains controversial. We hypothesized that the metabolic response to ketone supplementation differs between keto\u2010adapted and keto\u2010na\u00efve states. In this study, we investigated the effects of \u03b2\u2010hydroxybutyrate (BHB) supplementation in keto\u2010adapted mice. Mice were assigned to three groups: control diet (CON), ketogenic diet (KD), or KD with sodium \u03b2\u2010hydroxybutyrate supplementation (KD+BHB) for 6\u2009weeks. Chronic BHB supplementation in keto\u2010adapted mice (KD+BHB) further elevated circulating ketone levels compared to KD alone (2.63\u2009\u00b1\u20090.53 vs. 1.96\u2009\u00b1\u20090.34\u2009mM, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Despite significantly lower muscle glycogen content, both KD and KD+BHB groups maintained exercise capacity comparable to controls, demonstrating a glycogen\u2010thrifty effect. During exercise, both KD groups showed greater BHB utilization and glucose preservation compared to controls. Gene expression analysis revealed upregulation of fatty acid oxidation\u2010related genes across multiple tissues in KD+BHB mice, with more pronounced effects than KD alone. Additionally, KD+BHB mice showed increased AMPK phosphorylation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 vs. CON) and reduced mTOR activation (<jats:italic>p<\/jats:italic>\u2009=\u20090.058 vs. CON) in liver and skeletal muscle, creating a metabolic environment favoring fat utilization. These findings demonstrate that ketone supplementation in keto\u2010adapted status creates a glycogen\u2010thrifty state during exercise, suggesting metabolic context significantly influences responses to exogenous ketones.<\/jats:p>","DOI":"10.14814\/phy2.70583","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T03:12:35Z","timestamp":1758856355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ketone body supplementation in keto\u2010adapted mice reveals metabolic adaptations and glycogen\u2010independent exercise capacity"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-5759","authenticated-orcid":false,"given":"Sihui","family":"Ma","sequence":"first","affiliation":[{"name":"Faculty of Sport Sciences Waseda University  Tokorozawa Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate School of Sport Sciences Waseda University  Tokorozawa Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishan","family":"Tong","sequence":"additional","affiliation":[{"name":"Graduate School of Sport Sciences Waseda University  Tokorozawa Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-0982","authenticated-orcid":false,"given":"Yumiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Meguro\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-5809","authenticated-orcid":false,"given":"Katsuhiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences Waseda University  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