Abstract Breast cancer is still the leading cause of death in women among all cancer types. Obesity, a chronic low grade inflammatory disease, is a key contributor to the progression of breast cancer especially in women, post-menopause. Given the current understanding of cancer-related inflammation and associated microvesicles in restructuring the microenvironment, we hypothesized that adipocyte-derived cytokines and exosomes negatively impact breast cancer progression. By contrast, eicosapentaenoic acid (EPA), a dietary omega 3 polyunsaturated fatty acid and a well-established anti-inflammatory compound will reduce adipocyte-secreted pro-inflammatory factors, thereby reducing breast cancer progression. To test these hypotheses, we investigated the effects of conditioned media or exosomes from 3T3-L1 adipocytes or human mesenchymal stem cells (HMSC), treated +/- 100uM EPA on MCF7 and MDA-MB231 breast cancer cells for 24 – 72 h. Following treatment, changes in breast cancer cell gene expression were measured using RT-qPCR and glycolytic rate was measured using XFe24 Seahorse extracellular flux analyze. We observed that conditioned medium from HMSC significantly increased the mRNA expression levels of oncogenic genes such as signal transducer and activator of transcription 3 (STAT3), baculoviral IAP repeat-containing protein3 (BIRC3) known as cIAP2, and the lipogenic fatty acids synthase (FASN). In contrast, conditioned media from EPA-treated human adipocytes reduced the expression levels of these genes. Similarly, exosomes isolated from EPA-treated adipocytes showed a significant reduction in mRNA expression levels of STAT3 and cIAP2 in both cancer cell lines. Furthermore, glycolysis was significantly reduced in MCF7 but not MDA-MB231 cells incubated with 3T3-L1 adipocyte-conditioned medium pretreated with EPA for 24 hrs. Taken together, our data suggest that adipocytes play a significant role in promoting breast cancer progression by providing a microenvironment that increases survival and inflammation. EPA is a promising anti-inflammatory nutrient that may help reduce breast cancer cell inflammation and survival, possibly by modulating adipocyte-derived cytokines and exosomes in obesity and thus warrants further investigations. Citation Format: Arwa Aljawadi, Sara Alhaj, Suranganie Dharamawardhane, Shane Scoggin, Lauren Gollahon, Preethi Gunaratne, Naima Moustaid-Moussa. Eicosapentaenoic acid reduces effects of some adipocyte derived factors on breast cancer cell inflammation and glucose metabolism [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 244. doi:10.1158/1538-7445.AM2017-244