Date of Award

1-1-2013

Document Type

Open Access Thesis

Department

Exercise Science

First Advisor

James A Carson

Abstract

Cancer cachexia is a complex syndrome that induces skeletal muscle wasting and dysregulation of skeletal muscle metabolism. Alterations in area of myofibers and myofiber metabolic properties can significantly impact the function of skeletal muscle. The purpose of this study was to examine the effect of cachexia severity and resistance exercise training on frequency and area of selected myofiber metabolic characteristics during cachexia-induced myofiber atrophy. Male ApcMin/+ (Min) mice were studied during the progression of cachexia (16-20 weeks of age) and stratified into groups based on the severity of cachexia. For the second study, male Min mice performed resistance exercise (RE) for 7 sessions over 2 weeks during the initiation of cachexia. Myofiber area and myofiber metabolic properties were examined through histological analysis (H&E, SDH, and PAS) in the tibialis anterior (TA) muscle. Cachexia severity progressively decreased TA cross-sectional area and frequency of high SDH activity (OX) fibers however there was also a progressive increased frequency of high glycogen content (HG) fibers. Regardless of SDH activity, myofiber area was decreased with cachexia. In cachectic mice, RE increased high SDH activity fiber frequency and selectively induced hypertrophy of low SDH activity (GL) fibers, however there were no changes in frequency of high glycogen content fiber with RE. These results demonstrate that during the progression of cancer cachexia, there is progressive myofiber atrophy regardless of SDH activity, a decrease in frequency of OX fibers and increase frequency of HG fibers. RE is able to increase frequency of OX fibers and induce hypertrophy of GL fibers.

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