Date of Award

1-1-2012

Document Type

Campus Access Dissertation

Department

Exercise Science

First Advisor

James A Carson

Abstract

Cachexia is a complicated metabolic syndrome associated with underlying chronic disease and characterized by the loss of body weight and muscle mass. The condition is associated with elevated levels of pro-inflammatory cytokines such as IL-6, disrupted glucose and fat metabolism, and loss of muscle strength and function. There is a growing evidence for sexual dimorphism related to the development of cachexia. ApcMin/+ mouse is as an animal model of colorectal cancer that has been widely used to study intestinal and colon polyp formation and growth, the effect of exercise and nutritional intervention as well as the regulation and progression of cancer cachexia. Our laboratory previously showed that the male ApcMin/+ mouse developed loss of muscle mass, fat mass, and muscle function associated with chronically elevated circulating IL-6, disrupted glucose and fat metabolism, and the loss of oxidative capacity as the cachexia progressed. In contrast, the age-matched female ApcMin/+ mouse maintained relatively low levels of plasma IL-6 and glucose metabolism depite the reduction in muscle strength and function associated with the progression of cancer cachexia. Two weeks of IL-6 over-expression in the weight-stable female mouse did not induce the loss of muscle mass, muscle strength, and insulin resistance that was observed in the male mice. Although female mouse showed IL-6 dependency on the changes of body weight, muscle mass and muscle strength, they seemed to be less susceptible to the levels of plasma IL-6. Two weeks of resistance exercise training during the progression of cachexia was effective to counteract muscle mass loss by stimulating anabolic signaling via activation of mTOR pathway and attenuating catabolic signaling via reduction of AMPK activity.

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