First Advisor

Hayward, Reid

Document Type

Dissertation

Date Created

5-2019

Abstract

Colon cancer is third the most prevalent cancer in the United States in both men and women. However, it is also a largely preventable disease, as colorectal cancer (CRC) risk is increased by environmental factors such as poor diet and physical inactivity. Furthermore, CRC patients are highly susceptible to significant muscle wasting. Cachexia is classified as a multifactorial metabolic syndrome associated with impairments in immune function, fatigue, and overall weakness, that lead to increased morbidity and mortality. To date, multiple studies have shown that both aerobic and resistance training, individually, are highly effective in their ability to attenuate the deleterious effects of cachexia. However, little research has focused on the inclusion of a program that combines both modes of exercise, which may be more clinically relevant. The purpose of the study was to examine the effects of multiple modes of exercise training on markers of cachexia to determine if treadmill training (TM), resistance training (RT), or a combination of the two (TM+RT) can effectively attenuate cachexia. A secondary purpose was to examine the involvement of interleukin-6 (IL-6) in the muscle wasting process and to determine if exercise training would reduce markers of systemic inflammation. Six-week old male Balb/c mice were randomly selected to sedentary (SED; n = 24) or exercise (EX; n = 36) groups. Mice in the EX group were further randomized to either a treadmill training (TM; n = 12), resistance training (RT; n = 12), or a combination (TM+RT; n = 12) group. At 11 weeks of age, half of the SED animals and all EX animals were inoculated with C26 cells; all EX mice continued their respective exercise protocols. Animals were sacrificed at 14 weeks of age. Cachexia was assessed via body mass, gastrocnemius mass and CSA, forelimb grip strength, and systemic inflammation. Colon-26 carcinoma induced cachexia in SED+Tumor mice, as evident by significant decreases in body mass, gastrocnemius mass and CSA, declines in muscle function, and increases in systemic inflammation markers. Exercise, specifically RT, was able to provide significant improvements in all examined markers of cachexia, with the exception of relative body mass. Significant improvements also existed in TM+Tumor and TM+RT+Tumor in regard to gastrocnemius CSA and muscle function when compared to SED+Tumor. These data suggest that exercise training, regardless of mode are able to provide significant benefit to cachectic mice and this may be due, in part, to decreases in systemic inflammation.

Extent

76 pages

Local Identifiers

Wood_unco_0161D_10718

Rights Statement

Copyright is held by the author.

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