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Currently, there are no clear diagnostic criteria, its effects are irreversible, and it cannot be treated. Most patients progress undetected to late stages of cancer cachexia, stop responding to traditional treatment, and die without an effective intervention. While the literature has begun to characterize late (refractory) cachexia muscle metabolic changes, less is known about early changes that may precede obvious muscle dysfunction and wasting. Therefore, this investigation aimed to characterize early phase heart and skeletal muscle metabolic changes in a preclinical model of colorectal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Apc(min\/+) mouse spontaneously forms tumors along the intestinal tract and is a well\u2010accepted preclinical colorectal cancer model. To identify early changes in muscle metabolism during colorectal cancer development, heart and gastrocnemius tissues from 15\u2010week\u2010old male Apc(min\/+) and litter\u2010matched non\u2010carrier mice (wildtype) were analyzed by untargeted GC\/MS metabolomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the heart, metabolic pathways related to taurine\/hypotaurine metabolism; biosynthesis of unsaturated fatty acids; alanine, glutamate, and aspartate; arginine and proline; and arginine biosynthesis were affected by colorectal cancer. In skeletal muscle, metabolic pathways involving arginine biosynthesis; alanine, glutamate, aspartate, and proline metabolism were affected by cancer cachexia. Taken together, these data demonstrate altered arginine metabolism and proline metabolism in hearts and skeletal muscle of cachectic mice. Interestingly, cardiac muscle showed a non\u2010preferential fuel switch towards less energetically favorable glycolysis (vs. fatty acid metabolism) that coincided with cardiac dysfunction, while skeletal muscle exhibited glucose dysregulation and possible insulin resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data characterize early cardiac and skeletal muscle metabolic derangements that lead to muscle dysfunction and atrophy during colorectal cancer. Such data could help identify patients in early phases of cachexia or identification of cardiac and skeletal muscle specific therapeutic targets aimed at early intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.70290","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T09:33:49Z","timestamp":1758620029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Markers of Cardiac and Skeletal Muscle Metabolic Derangement in the Apc(min\/+) Male Mouse"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-4537","authenticated-orcid":false,"given":"Traci L.","family":"Parry","sequence":"first","affiliation":[{"name":"Department of Kinesiology University of North Carolina Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Nutrition, and Dietetics, and the University of Northern Colorado Cancer Rehabilitation Institute University of Northern Colorado  Greeley Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Garritson","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Nutrition, and Dietetics, and the University of Northern Colorado Cancer Rehabilitation Institute University of Northern Colorado  Greeley Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Muehlbauer","sequence":"additional","affiliation":[{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke Molecular Physiology Institute Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louisa","family":"Tichy","sequence":"additional","affiliation":[{"name":"Department of Kinesiology University of North Carolina Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason T.","family":"Brantley","sequence":"additional","affiliation":[{"name":"Department of Kinesiology University of North Carolina Greensboro  Greensboro North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Bain","sequence":"additional","affiliation":[{"name":"Sarah W. 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