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Muscle Metabolism in the Apc(min/+) Male Mouse
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  • Traci L. Parry,
  • Nicole Wood,
  • Jacob Garritson,
  • Michael J. Muehlbauer,
  • Jason T. Brantley,
  • Louisa Tichy,
  • James R. Bain,
  • Reid Hayward
Traci L. Parry
UNC Greensboro Department of Kinesiology

Corresponding Author:[email protected]

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Nicole Wood
University of Northern Colorado Department of Biological Sciences
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Jacob Garritson
University of Northern Colorado Department of Biological Sciences
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Michael J. Muehlbauer
Duke University Department of Biology
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Jason T. Brantley
UNC Greensboro Department of Kinesiology
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Louisa Tichy
UNC Greensboro Department of Kinesiology
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James R. Bain
Duke University Department of Biology
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Reid Hayward
University of Northern Colorado Department of Biological Sciences
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Abstract

Cancer cachexia is a metabolic and wasting disease that occurs in up to 80% of cancer patients. 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. To determine the effect of tumor bearing on muscle metabolism, heart and gastrocnemius tissues from 15-week-old male Apc(min/+) and litter-matched non-carrier mice (wildtype) were analyzed by untargeted GC/MS metabolomics. The Apc(min/+) mouse spontaneously forms tumors along the intestinal tract and is a well-accepted preclinical model of colorectal cancer. 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 tumor bearing. 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-preferential 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. These data shed important light on metabolic derangements associated with cancer cachexia that lead to muscle dysfunction and atrophy. Such data may provide a valuable stepping stone in understanding the metabolic consequence of cancer cachexia to assist in identification of therapeutic targets.