{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T04:04:24Z","timestamp":1775621064371,"version":"3.50.1"},"reference-count":74,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T00:00:00Z","timestamp":1749945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Low cardiorespiratory fitness increases the risk for cardiometabolic disease. Endurance exercise training promotes cardiorespiratory fitness and improves cardiometabolic risk factors, but with great heterogeneity. Here, we tested the hypothesis that the metabolic phenotype imparted by low parental (inborn) cardiorespiratory fitness would be overcome by early\u2010life exercise training, and that exercise adaptations would be influenced in part by inborn fitness. At 26\u00a0days of age, male and female rat low\u2010capacity runners (LCR,\n                      <jats:italic>n\u00a0=\u00a0<\/jats:italic>\n                      20) and high\u2010capacity runners (HCR,\n                      <jats:italic>n\u00a0=\u00a0<\/jats:italic>\n                      20) generated by artificial selection were assigned to either sedentary control (CTRL,\n                      <jats:italic>n\u00a0=\u00a0<\/jats:italic>\n                      10) or voluntary wheel running (VWR,\n                      <jats:italic>n\u00a0=\u00a0<\/jats:italic>\n                      10) for 6\u00a0weeks. Post\u2010intervention, whole\u2010body metabolic phenotyping was conducted, and the respiratory function of isolated skeletal muscle and liver mitochondria was assayed. Transcriptomic and proteomic profiling of these tissues was performed using RNA\u2010sequencing and mass spectrometry, respectively. Daily VWR volume was 1.8\u2010fold higher in HCR\u2010VWR compared to LCR\u2010VWR. In LCR, VWR reduced adiposity and enhanced glucose tolerance, coincident with elevated total energy expenditure. Although intrinsic skeletal muscle mitochondrial respiratory function was unchanged, estimated skeletal muscle oxidative capacity increased in VWR groups. In liver mitochondria, VWR increased both maximal oxidative capacity and ATP\u2010linked respiration only in HCR. Transcriptomic and proteomic profiling revealed extensive remodelling of skeletal muscle and liver tissue by VWR, elements of which were both shared and distinct based on inborn fitness. Early\u2010life exercise partly offsets the metabolic effects of low inborn fitness, but molecular adaptations to VWR are dependent on inborn fitness, with potential implications for personalized exercise medicine.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16803-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Low cardiorespiratory fitness is a heritable trait associated with increased risk for cardiometabolic disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Endurance exercise training promotes cardiorespiratory fitness and metabolic health but how genetic (inborn) fitness influences exercise\u2010induced adaptations is unclear.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We used rats selectively bred for low (LCR) or high running capacity (HCR) to test whether: (1) early\u2010life voluntary wheel running (VWR) could offset poor metabolic health in LCR rats and (2) inborn fitness modulates adaptations to VWR.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>VWR improved body composition and glucose tolerance in LCR rats but did not alter mitochondrial respiratory function.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Molecular analyses revealed that VWR induced shared and distinct changes in skeletal muscle and liver depending on inborn fitness, highlighting individualized biological responses.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings suggest that genetic factors linked to fitness influence how the body adapts to exercise, with implications for personalized exercised medicine.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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