Abstract 910: High dietary fat promotes inflammation and intestinal neoplasia, independently of diet-induced obesity, in B6.ApcMin/+ congenic-consomic mouse strains

Abstract

Abstract Obesity and high fat (HF) diet are associated with increased risk of colon cancer. However, assessing their independent contributions to intestinal carcinogenesis is difficult due to their close association in humans. We utilized Chromosome Substitution Strains (CSSs) in combination with the B6.ApcMin/+ mouse model of intestinal cancer to generate Congenic-Consomic Strains (C-CSs). Using C-CSs, we tested whether a HF diet promotes the development of intestinal cancer, independent of obesity, and found that dietary fats are strong and independent determinants of polyp formation. CSSs, which have contrasting responses to a HF diet, were used to construct C-CSs that were susceptible to intestinal cancer, but were either resistant or susceptible to diet-induced obesity, depending on the substituted A/J chromosome. A2.ApcMin/+ (obese), A7.ApcMin/+ (lean), and A17.ApcMin/+ (lean) mouse strains were maintained on diets high or low in coconut oil (HFCoco and LFCoco, respectively). If obesity is crucial in polyp formation, all obese strains should develop more polyps than the lean strains. In contrast, if diet is important, we expected to find an increase in polyp number in all strains fed the HFCoco diet, independent of their susceptibility to diet-induced obesity. Polyp numbers were significantly increased in all strains after 60 days exposure to the HFCoco diet, regardless of obese or lean status, suggesting that a HF diet promotes polyp development. Polyp numbers were also significantly higher in B6.ApcMin/+ after similar exposure to a high fat corn oil (HFCorn) diet. We measured levels of circulating inflammatory factors and showed that adiponectin is decreased and leptin, interleukin (IL)-1beta and IL-6 are increased in B6.ApcMin/+ fed either of the HF diets compared to mice fed the corresponding LF control diets, implicating a role of inflammation in diet-induced intestinal neoplasia. With the novel C-CS systems, we were able to elucidate complex diet-gene interactions involved in intestinal carcinogenesis and provide evidence for a crucial role of a HF diet in the development of intestinal polyps. These dietary studies have implications for both prevention and non-invasive treatment of intestinal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 910. doi:10.1158/1538-7445.AM2011-910