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The Effect of Metformin, Flutamide and Dietary Nicotinic Acid on Dyslipidemia and Cardiometabolic Risk in the JCR:LA-­cp Rodent Model of PCOS Open Access


Other title
polycystic ovary syndrome
nicotinic acid
Type of item
Degree grantor
University of Alberta
Author or creator
Kupreeva, Maria
Supervisor and department
Vine, Donna (Agricultural, Food and Nutritional Science)
Examining committee member and department
Proctor, Spencer (Agricultural, Food and Nutritional Science)
Ghosh, Mahua (Medicine)
Jacobs, Rene (Agricultural, Food and Nutritional Science)
Lehner, Richard (Pediatrics)
Department of Agricultural, Food, and Nutritional Science
Nutrition and Metabolism
Date accepted
Graduation date
Master of Science
Degree level
Polycystic ovary syndrome (PCOS) is a highly prevalent metabolic-endocrine disorder affecting up to 18% of adolescent and adult females in their reproductive years. PCOS is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes. Atherogenic dyslipidemia occurs in 70% of PCOS patients, however at present the independent role of testosterone and insulin in modulating lipid metabolism in PCOS is not understood. Currently, there is no single therapy that is safe and effective to improve plasma lipids and cardiometabolic risk in PCOS. The primary aim of this thesis was to determine the effect of the insulin sensitizer, metformin, and the androgen receptor blocker, flutamide, and a lipid-lowering vitamin, nicotinic acid, on insulin and glucose, lipid and apoB-lipoprotein metabolism in the JCR:LA-cp rodent model of PCOS. The results showed metformin improved fasting plasma insulin and HOMA-IR, and attenuated intestinal chylomicron-cholesterol secretion and this was concomitant with changes in insulin signaling and lipogenic gene expression. Flutamide reduced fasting plasma TG, apolipoprotein (apo) B48 and apoB100, as well as intestinal TG secretion, but there was no effect on mRNA expression of lipogenic genes. Nicotinic acid treatment alone improved postprandial plasma insulin concentrations and tended to decrease intestinal chylomicron-apoB48 secretion. Addition of metformin reduced fasting plasma insulin, glucose and HOMA-IR, insulin and glucose response to a ‘meal tolerance test’ and tended to lower fasting plasma TG and apoB48 concentrations. Collectively, the results from these studies demonstrate: i) the androgen receptor and testosterone mediate regulation of lipid and lipoprotein metabolism in the liver and intestine and this is independent of insulin, ii) nicotinic acid has beneficial effects on insulin-glucose metabolism and may have the potential to target dyslipidemia in PCOS conditions, as demonstrated in the JCR:LA-cp rodent model of PCOS.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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