Effects of dietary polyunsaturated fatty acids on colorectal cancer and the development of the total Western diet-2.

摘要

ABSTRACT.;The Effect of Dietary Polyunsaturated Fatty Acids on Colorectal Cancer and the Development of.;the Total Western Diet-2.;by.;Sara Kellen, Master of Science.;Utah State University, 2014.;Major Professor: Dr. Korry Hintze.;Department: Nutrition, Dietetics, and Food Science.;The Western diet is characterized by the consumption of foods high in omega-6 (n-6) fatty acids, leading to high ratios of omega-6 to omega-3 (n-3) fatty acids. This dietary pattern has been hypothesized to cause higher incidences of colorectal cancer (CRC) due to the pro-inflammatory nature of n-6 fatty acids. Using an azoxymethane and dextran sodium sulfate (AOM+DSS) induced inflammatory model, mice were fed identical diets, varying only in dietary polyunsaturated fatty acid (PUFA) concentration and n-6:n-3 ratio. They included 1.) AIN-93G, control diet, containing 7% (kcal) dietary PUFA 7:1 n-6:n-3 ratio, 2.) 2.5% dietary PUFA 1:1 n-6:n-3 ratio, 3.) 2.5% PUFA 20:1 n-6:n-3, 4.) 10% PUFA 1:1 n-6:n-3, and 5.) 10% PUFA 20:1 n-6:n-3. Mice fed the AIN-93G and the 2.5% PUFA with a 1:1 n-6:n-3 ratio resulted in significantly higher colon tumor multiplicity (p-value < 0.0001) compared to the other treatments. Additionally the ratio n-6:n-3 had a significant effect on tumor size. Mice fed diets with a PUFA ratio of 1:1 had significantly larger tumors than mice fed diets with a PUFA ratio of 20:1. Using colon length as a measure of inflammation, no significant differences were found between diet treatments. Results from our study suggest dietary PUFA profile influences the etiology of CRC.;Rodents are commonly used as pre-clinical animal models to study various human diseases. Typically, mice are fed a purified diet formulated to optimize the animal's growth and health. However, these diets are considerably different than the average American diet. Hintze and colleagues developed the Total Western Diet (TWD), which matches both the macro- and micronutrient content of the average American diet, giving researchers a rodent diet more suitable for studying colon health and related diseases. The TWD-2 was designed to improve upon the TWD by incorporating the complex dietary components of whole-foods known to impact gut health. The TWD-2 is currently the only whole-food-based rodent diet that emulates both the macro- and micronutrients of the average American diet. Initiating studies using the TWD-2, in place of the AIN diets, will hopefully make the rodent a better model for human colorectal cancer research.