Abstract 2859: Differential effects of specific dietary fat sources on inflammation and intestinal tumorigenesis.

Abstract

Abstract Diet-induced obesity (DIO) and metabolic syndrome (MetS) are important factors that contribute to the development and progression of cancer, especially colon cancer. DIO and MetS have reached epidemic proportions in the United States and are heavily influenced by diets high in saturated and omega-6 polyunsaturated fatty acids. Using the ApcMin/+ model of intestinal neoplasia and diets constructed from 58% coconut, corn or olive oils, we demonstrate that high amounts of dietary fats can have differential effects on DIO and MetS, as well as on intestinal tumorigenesis when compared to ApcMin/+ fed corresponding calorically equivalent control diets that contained 10% fat from these same sources. Specific sources of dietary fat lead to more rapid tumor progression, elevated polyp number and mass, as well as increased mortality, thus eliciting a detrimental impact on disease outcome, while others fail to induce an increase in polyp burden and reduce cancer severity in mice with genetic predisposition to intestinal neoplasia. We demonstrate that the tumor promoting effects of different fats are associated with systemic and local intestinal inflammation and that excess nutritional richness from specific sources can increase pro-inflammatory factors such as IL-6, IL-1β, TNFα, COX-2. Adipokines, such as adiponectin and leptin, are differentially modulated in response to different fat sources. Short (3 day) dietary exposure is sufficient to induce inflammation and tumorigenesis before the onset of DIO or MetS, suggesting a potent effect of diet on intestinal immunity. Additionally, we demonstrate a novel mechanism for the innate immunity in diet-induced intestinal cancer. We show that pharmacological and genetic inhibition of innate immunity factors can significantly reduce polyp number and mass in ApcMin/+. These results suggest that nutritional modification may be a useful approach to alter intestinal and systemic inflammation with potential preventative value for use in colon tumorigenesis and that diet, immunity and cancer are intrinsically related. Citation Format: Stephanie K. Doerner, Elaine S. Leung, Justine S. Ko, Joseph H. Nadeau, Nathan A. Berger. Differential effects of specific dietary fat sources on inflammation and intestinal tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2859. doi:10.1158/1538-7445.AM2013-2859