Date of Award

Summer 2019

Document Type

Open Access Thesis

Department

Biological Sciences

First Advisor

E. Angela Murphy

Abstract

Obesity is considered a major public health concern worldwide due to the increased incidences of metabolic dysfunction and cancer risk. The obese state is, in part, attributable to the overconsumption of calorie-dense foods commonly seen in a standard Western diet, which aids in the progression of chronic, lowgrade inflammation. The role of estrogen varies depending on menopausal status, where estrogen deficiency coupled with increased visceral fat associated with post-menopause leads to increased secretions of pro-inflammatory adipokines and cytokines. However, the presence of estrogen in a premenopausal state has been shown to attenuate the pro-inflammatory response, which has been demonstrated when estrogen replacement is administered to ovariectomized (OVX) mice. The purpose of this study was to determine if various pro-inflammatory cytokines secreted by adipose tissue influences cancer growth and if ovarian status affects this response. Methods: The study utilized a diet-induced model of obesity, where 8-week-old intact female, OVX female, and male mice were assigned to either a 40% high-fat diet (HFD) or a purified control low-fat diet (LFD) for 21 weeks. The ovaries of the OVX female group were removed in order to study the role of ovarian status in obesity and cancer initiation. To determine if pro-inflammatory cytokines associated with increases in body weight and fat mass influence cancer proliferation, adipose tissue-conditioned media (AT-CM) obtained from each dietary group was supplemented to MC38 colon cancer cells and a proliferation assay was performed. Results: An obese phenotype in mice fed a HFD was achieved and detectable increases in WBC, LYM, MON, and PLT count in the blood associated with obesity were identified. There were no diet effects discovered in the concentration of pro-inflammatory cytokines circulating in the plasma; however, a main effect of HFD (p<0.05) exhibited increased secretions of IL-1β and IL-6 from the AT-CM when comparing the intact and OVX female groups. No significant differences were discovered in the cell proliferation assay after treatment with AT-CM. Conclusion: HFD feedings resulted in significant increases in body weight and fat mass. Secreted levels of pro-inflammatory cytokines were detected in the AT-CM in the intact and OVX females. There was no difference detected in the cell proliferation assay after 24hrs.

Rights

© 2019, Meredith Smith Carson

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