Date of Award
Open Access Dissertation
James A. Carson
Cachexia is a devastating a life-threatening condition that occurs secondary to underlying disease including cancer, AIDS, COPD and comprises severe loss of muscle and fat mass. Muscle mass atrophy and wasting with cachexia is especially dire, as skeletal muscle mass is associated with quality of life, functionality, and ability to respond to chemotherapeutics. While much investigation has been done in the male animal to elucidate the inflammatory pathways and muscle signaling underlying cachexia, very little work has occurred in the female. The overall purpose of this study is to determine if ovarian function can alter cachexia progression in the female ApcMin/+ mouse through IL-6 signaling and the regulation of skeletal muscle metabolism. Specific aim #1 sought to determine the relationship between circulating IL-6 and cancer cachexia progression in the female ApcMin/+ mouse. We found that the canonical IL-6 signaling pathway that is a key point of regulation in the male ApcMin/+ is dysregulated in the female, and that IL-6 levels do not correlate with body weight loss and severity as they do in the male. Specific aim #2 sought to determine whether ovarian function loss or dysfunction could influence IL-6 regulation of cancer cachexia progression in the female ApcMin/+ mouse. The loss of ovarian function due to disease did cause an increase in Il-6-related and other inflammation, while ovariectomy (OVX) alleviated much of the cachexia-related inflammation. Specific aim #3 sought to determine whether cachexia-induced skeletal muscle metabolic dysfunction is regulated by ovarian function in the female ApcMin/+ mouse. As expected, measures of protein degradation and mitochondrial dysregulation increased with increasing cachexia severity; however, OVX brought these measures back towards baseline. These findings provide insight into the intricate regulation of cachectic pathways by ovarian endocrine function, and will provide potential targets for therapeutics interventions for cancer cachexia.
Hetzler, K. L.(2015). The Role of Ovarian Function in the Progression of Cachexia in the APCMIN/+ Mouse. (Doctoral dissertation). Retrieved from http://scholarcommons.sc.edu/etd/3241