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Myofiber degeneration/regeneration is induced in the cachectic Apc^Min/+ mouse

¹Division of Applied Physiology, Exercise Science Department, ²Department of Biological Sciences, and ³Center for Colon Cancer Research, University of South Carolina, Columbia, South Carolina

Submitted 30 June 2005 ; accepted in final form 28 July 2005

Cachexia is characterized as an inflammatory state induced by the cancer environment, which is accompanied by the loss of muscle and fat mass. Well-investigated mechanisms of cachexia include the suppression of myofiber protein synthesis and the induction of the protein degradation. However, it is not well characterized whether chronic inflammation during cachexia induces myofiber degeneration, which contributes to muscle mass loss and decreased functional capacity. The purpose of this study was to determine whether Apc^Min/+ mice, which demonstrate a chronic systemic inflammatory state due to an intestinal tumor burden, undergo cachexia and whether the myofibers exhibit signs of degeneration and/or regeneration. Six-month-old female Apc^Min/+ body weight decreased 21% compared with C57BL/6 mice and was not the result of blunted growth. Apc^Min/+ gastrocnemius muscle was reduced 45%, and soleus mean fiber cross-sectional area decreased 24% vs. C57BL/6 mice. Soleus muscle morphology demonstrated pathology of myofibers undergoing degeneration and/or regeneration. These data demonstrate that the Apc^Min/+ mouse becomes cachectic by 6 mo of age and that skeletal muscle degeneration and regeneration may be related to the muscle loss.

muscle wasting; colon cancer; inflammatory cytokines

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