Exploring the Role of Mitochondria in Muscle Weakness and Atrophy in a Mouse Model of Cancer Cachexia

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Date

2020-11-13

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Delfinis, Luca Joseph

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Abstract

Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass. The focus of this thesis was to determine the degree of skeletal muscle mitochondrial bioenergetic dysfunction in a preclinical model of cancer cachexia as this may reveal impaired energy homeostasis as a mechanism underlying muscle atrophy and muscle weakness. To do this, we used the C26 cancer cachexia model and evaluated mitochondrial bioenergetics in both the quadriceps and diaphragm. Our findings reveal that effects of C26 cancer on mitochondrial bioenergetic differs between diaphragm and quadriceps. In addition, this thesis reports a unique finding whereby mitochondrial ADP sensitivity is increased in C26 cancer cachectic skeletal muscle, suggesting that cancer improves the ability of muscle mitochondria to respond to changes in energy demand. Moreover, these findings also suggest that mitochondria may be more uncoupled in cancer cachexia.

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Kinesiology

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