Consumption of the fish oil high fat diet uncouples obesity and tumor growth through induction of reactive oxygen species in pro-tumor macrophages

• Published in: The Journal of immunology (1950) 2020-05, Vol.204 (1_Supplement), p.240-240.14
• Main Authors: Li, Bing, Jin, Rong, Hao, Jiaqing
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.240.14

It is clear that obesity is associated with increased risk of many types of cancer. However, obesity can be induced by various high fat diets (HFDs) from different fat sources. It remains unknown whether fatty acid composition in different HFDs influences obesity-associated tumor development. Herein we report that consumption of either a cocoa butter or fish oil HFD induced similar obesity in mouse models. While obesity induced by the cocoa butter HFD was associated with accelerated tumor growth, consumption of the fish oil HFD uncoupled obesity from increased tumor growth and exhibited a decrease in pro-tumor macrophages. Interestingly, compared to FA components in both HFDs, n-3 FAs rich in the fish oil HFD induced significant production of reactive oxygen species (ROS) and macrophage cell death. Moreover, we found that A-FABP expression in the pro-tumor macrophages facilitated n-3 FA intracellular transportation and mitochondrial FA oxidation. A-FABP deficiency diminished n-3 FA-mediated ROS production and macrophage cell death both in vitro and in vivo. Altogether, our results demonstrate a novel mechanism by which n-3 FAs induce ROS-mediated pro-tumor macrophage cell death in an A-FABP dependent manner. This study provides mechanistic insights into dietary supplementation with fish oil for cancer prevention and puts forwards a new concept that not all HFDs leading to obesity are tumorigenic.