{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:02:22Z","timestamp":1790240542753,"version":"4.1.0"},"reference-count":113,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Repeated heat exposure may promote adaptive remodeling or cumulative tissue burden depending on thermal dose, but its graded molecular and functional consequences during recovery remain unclear. We examined whether repeated moderate (39\u00b0C) and severe (41\u00b0C) whole\u2010body hyperthermia produce distinct skeletal muscle trajectories involving mitochondrial dynamics, proteostasis, contractile gene programming, and motor behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male Swiss mice underwent 15\u2010min daily whole\u2010body heat exposure for 7\u2009days at 39\u00b0C or 41\u00b0C core temperature and were assessed immediately or after 7\u2009days of recovery. Motor and behavioral outcomes were evaluated using open\u2010field, elevated plus maze, grip strength, and rotarod tests. Gastrocnemius muscle was analyzed by qRT\u2010PCR, immunoblotting, and immunofluorescence for mitochondrial biogenesis, dynamics, mitophagy, proteostasis, and contractile phenotype markers. Cerebellar HSP60\/HSP70 immunoreactivity and serum corticosterone were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At 39\u00b0C, recovery induced coordinated mitochondrial biogenesis and balanced fission\u2010fusion transcript upregulation. At 41\u00b0C, acute\n                      <jats:italic>Ppargc1a<\/jats:italic>\n                      induction (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) was followed by recovery\u2010phase mitophagy and oxidative\u2010response gene upregulation. Gastrocnemius ERK phosphorylation increased preferentially during 39\u00b0C exposure (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). HSP60 progressively declined across recovery groups, whereas HSP70 increased only after 41\u00b0C recovery (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Grip\u2010related neuromuscular performance was impaired at 41\u00b0C in both phases (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), while rotarod performance remained intact. Cerebellar HSP70 was strongly suppressed by heat exposure (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and partially restored after 39\u00b0C recovery. Principal component analysis without group labels reproduced this divergence, yielding a dose\u2009\u00d7\u2009phase interaction axis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20095.7\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Moderate hyperthermia supports adaptive mitochondrial remodeling, whereas severe hyperthermia promotes stress\u2010related quality control, proteostatic strain, contractile suppression, and reduced grip\u2010related neuromuscular performance.<\/jats:p>\n                  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