{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:04:57Z","timestamp":1772982297507,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004890","name":"Wageningen University and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colon cancer (CC), the third most common cancer worldwide, is accompanied by cachexia in 30% of patients. Its associated muscle loss directly impairs therapeutic response and survival. Early intervention is crucial, yet the underlying mechanisms of early\u2010stage muscle dysfunction remain unclear. This study investigates mitochondrial function in skeletal muscle across different CC stages to identify early metabolic alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The present study investigated mitochondrial function in\n                      <jats:italic>rectus abdominus<\/jats:italic>\n                      muscle biopsies from 30 patients with primary CC (83% male, mean age 67\u2009\u00b1\u20098\u2009years), 10 patients with colorectal cancer with liver metastases (50% male, mean age 69\u2009\u00b1\u20096\u2009years), and 17 age\u2010matched controls (65% male, mean age 66\u2009\u00b1\u20097\u2009years). Mitochondrial oxygen consumption was assessed using high\u2010resolution respirometry, and transcriptional profiles were analysed via RNA sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with primary CC exhibited reduced complex I activity compared to controls (9.02 vs. 12.47\u2009pmol\/s\/mg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), accompanied by transcriptional upregulation of oxidative phosphorylation (OXPHOS)\u2010related genes. In contrast, patients with liver metastases showed more severe mitochondrial dysfunction, with reductions in both complex I (7.38 vs. 9.65\u2009pmol\/s\/mg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and complex II (8.36 vs. 19.73\u2009pmol\/s\/mg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), but without the compensatory transcriptional upregulation seen in primary CC. These mitochondrial impairments occurred before detectable declines in physical function or systemic inflammation (C\u2010reactive protein, albumin).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal stage\u2010specific mitochondrial dysfunction in CC, with early complex I impairment and a transient transcriptional adaptation in primary CC. These alterations precede clinical cachexia, suggesting mitochondrial dysfunction as a potential early biomarker for cancer\u2010induced muscle loss and a target for early intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70117","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:44:37Z","timestamp":1762944277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary\u2010Stage Colon Cancer Impairs Muscle Energy Metabolism by Suppressing Mitochondrial Complex I Activity"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-8631","authenticated-orcid":false,"given":"Xiaolin","family":"Li","sequence":"first","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University  Wageningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"van der 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Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mieke","family":"Poland","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University  Wageningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaap","family":"Keijer","sequence":"additional","affiliation":[{"name":"Human and Animal Physiology Wageningen University  Wageningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renger\u00a0F.","family":"Witkamp","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University  Wageningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tjarda","family":"van Heek","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition and Health Wageningen University  Wageningen the Netherlands"},{"name":"Gelderse Vallei Hospital  Ede the 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