Abstract PS8-27: Consumption of a high-fat diet rich in linoleic acid promotes mammary tumor growth

Abstract Consumption of high-fat diets rich in linoleic acid promotes mammary tumor growth Rong Jin1, Jiaqing Hao1, Edward Sauter2, Bing Li1 1Department of Microbiology and Immunology, University of Louisville, Louisville, KY2Hartford Healthcare Cancer Institute, Hartford, CT *To whom correspondence should be addressed: Bing Li, Department of Microbiology and Immunology, University of Louisville, 505 South Hancock Street, Louisville, KY, 40202. Telephone: 502-852-2678. Email: b.li@louisville.edu. AbstractBackground: The most recent Dietary Guidelines in 2015-2020 for Americans from the U.S. Department of Health and Human Services (DHH) and U.S. Department of Agriculture (USDA) recommends a healthy eating pattern with more oils but less saturated fats. Oils predominantly consist of unsaturated fats with either monounsaturated or polyunsaturated fatty acids (FAs). As high fat diets (HFDs) contribute to obesity, which increases the risk of breast cancer, in this report we evaluate whether the consumption of HFDs rich in different unsaturated fatty acids induces similar degrees of obesity and further determines the impact of different oils on mammary tumor growth using our unique murine mouse models. Hypothesis: Consumption of different oils impacts obesity-associated mammary tumor development. Methods: Weaned C57BL/6 wild type (WT) mice and epidermal fatty acid binding protein (E-FABP)-deficient (genetically depleted E-FABP) female mice were randomly grouped and fed either a safflower oil HFD (45% fat, rich in 18:2 polyunsaturated FAs) or an olive oil HFD (45% fat, rich in 18:1 monounsaturated FAs), or a control low fat diet (LFD). After 5 months on the diets, E0771 mammary tumor cells (0.5 × 106/mouse) were injected into the mammary fat pad and tumor volume was measured at 3-day intervals for tumor growth. Immune cell phenotype and functions were evaluated before and after tumor injection. The student’s t-test and/or ANOVA were used to compare immune cell function, obesity and tumor sizes in WT and E-FABP-/- mice, respectively. Results: Compared to the LFD diet, consumption of either safflower oil HFD or olive oil HFD was able to induce a similar degree of mouse obesity in WT mice. E-FABP deficiency has no obvious impact on HFD-induced mouse weight increase. Interestingly, while safflower oil-induced obesity significantly increased mammary tumor growth, olive oil-induced obesity did not promote mammary tumor growth when compared to LFD-fed lean mice. Immunophenotypic and functional analyses showed that mice on the safflower oil diet exhibited lower numbers of CD8+ T cells with reduced production of TNFa than mice on the olive oil diet or LFD. Moreover, safflower oil-associated tumor growth was compromised in mice genetically lacking of E-FABP expression. Mechanistically, E-FABP expression in T cells, especially in CD8+ T cells, mediated 18:2 linoleic acid-induced ROS production and T cell death, thus leading to impaired anti-tumor immunity in safflower oil-fed obese mice. Impact: Although oils are healthy dietary components as recommended by DHH and USDA, different oils exhibit diverse immunoregulatory effects in vivo. Overconsumption of oils with 18:2 FAs may cause obesity-associated breast cancer development. Citation Format: Rong Jin, Jiaqing Jiaqing, Di Yin, Yanmei Yi, Hua Yuan, Satuer Edward, Bing Li. Consumption of a high-fat diet rich in linoleic acid promotes mammary tumor growth [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-27.