Connor, Michael K.2017-07-272017-07-272016-11-042017-07-27http://hdl.handle.net/10315/33438Breast cancer continues to be the number one cause of new cancer cases and second in mortality rate in Canadian women. For almost 50 years now researchers have shown a statistical link between obesity and breast cancer. Although adipose tissue in the past was considered an inert storage depot, we now know it produces and secretes the adipokines adiponectin (ADIPO) and leptin (LEP). Lean individuals have been shown to have higher circulating levels of ADIPO and lower levels of circulating LEP, while the opposite is found in obese individuals, which ultimately alters the ratio between the two adipokines. Adiponectin has been shown to bind to its membrane receptor AdipoR1 and activate the cell signalling pathway AMPK, stabilizing the cell cycle inhibitor protein p27, leading to cell cycle arrest. Leptin on the other hand binds to its membrane receptor Ob-Rb and activates the Akt signaling pathway, increasing the cytoplasmic localization of p27, leading to cell proliferation. The purpose of this thesis was to look at altering this ADIPO:LEP ratio through diet, physical activity and nutraceutical methods to determine if an altered secretome secretion profile could alter the adipose-dependent effects of obesity on breast cancer cell proliferation. The results show that any intervention that led to an alteration of the ratio between ADIPO:LEP ultimately leads to varying degrees of cell cycle arrest in MCF7 breast cancer cells depending on diet, volume of physical activity and nutraceutical intervention. I show that regardless of menopausal status, the ADIPO:LEP ratio remained as a reliable and consistent predictor of the proliferative tumor growth microenvironment created by obese adipose tissue. Additionally, stabilizing ADIPO signaling through AdipoR1 abolishes the proliferative effects of an obese adipose-dependent growth microenvironment on breast cancer cells. The implications of this thesis is that adipose tissue presents a stable and predictable component of a patients physiology providing possible novel treatment avenues for obesity-linked cancers.enAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.Molecular biologyElectronic Thesis or Dissertation2017-07-27ObesityAdipose TissueBreast CancerPhysical ActivityAdiponectinLeptin