Abstract 245: Dietary long-chain omega-3 fatty acids reduce adipose inflammation in mammary tissue of mice fed moderate fat-isocaloric diets

Increased adipose tissue Inflammation and breast density; including ductal epithelial hyperplasia have been associated with increased risks for breast cancer. Omega 6 (ω6) and omega 3 (ω3) fatty acids (FAs); serve as substrates for pro-inflammatory and inflammation resolving mediators respectively, emphasizing the potential regulatory role for dietary intake of these FAs in inflammation. Western diets have a ω6:ω3 FA ratio of >15:1 with low levels of long-chain (LC)-ω3FA. White adipose tissue inflammatory foci, characterized by crown-like structures (CLS) consisting of dead adipocytes and adjacent macrophages in breast tissue have been related to breast cancer risk in overweight and obese women presumably by the obesity-inflammation-aromatase axis. However, a role of dietary ω6:ω3 FA in adipose inflammation, independent of obesity is not clear. Herein, we examined effects of dietary ω6:ω3 ratio on the mammary tissue microenvironment and adipose inflammation using a moderate fat, iso-caloric diets, and pair-fed model. The LieberDeCarli diet containing 21:1 ratio of ω6:ω3 FA was used as a ω6 diet, whereas encapsulated fish oil containing a 3:1 ratio of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid was used to decrease ω6:ω3 ratio to 0.7:1 in the ω3 diet. Both iso-caloric diets contained 35.5% of calories derived from fat and were pair-fed to maintain iso-intake. Female BALB/c mice were established on the ω6 and ω3 diets for 10 weeks and weight gain and diet consumption monitored. There were no differences in the volume of diet consumed and weight gain between dietary groups. At autopsy, mammary fat pads (MFP) were collected and analyzed for fatty acid composition, histopathology, epithelial proliferation and macrophage infiltration. Arachidonic acid (AA) levels in the MFPs were not different between the groups but EPA and DHA were absent in the MFPs from the ω6 diet fed mice. Whereas, (2.41+/- 0.5) mole% of EPA and (1.52+/-0.29) mole% of DHA were detected in MFP of ω3 diet fed mice. The MFP of ω6 diet fed mice had significantly increased areas of unilocular adipocytes relative to adipocytes of the ω3 group. Similarly, ω6 diet fed mice had increased connective tissue in the ductal stroma, significantly higher numbers of proliferating cells in the ductal epithelium, as well as in adipose tissue area of MFP. In addition, ω6 diet fed mice had a significant increase in the numbers of CLS in mammary adipose tissue. In summary, our studies demonstrated that despite the comparable levels of AA in MFP in both of groups, the presence of LC-ω3 FA (EPA and DHA) was able to reduce inflammation in the MFP of ω3 diet fed mice, thus regulating the MFP microenvironments by reducing macrophage infiltration and ductal epithelial proliferation in an obesity-independent manner. Citation Format: Saraswoti Khadge, Geoffrey M. Thiele, John Graham Sharp, Lynell W. Klassen, Timothy R. McGuire, Michael J. Duryee, Holly C. Britton, Alicia J. Dafferner, Jordan Beck, Paul Black, Concetta C. DiRusso, James E. Talmadge. Dietary long-chain omega-3 fatty acids reduce adipose inflammation in mammary tissue of mice fed moderate fat-isocaloric diets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 245. doi:10.1158/1538-7445.AM2017-245