Obesity is associated with increased risk of many types of cancer and can be induced by various high-fat diets (HFD) from different fat sources. It remains unknown whether fatty acid composition in different HFD influences obesity-associated tumor development. Here 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 mammary tumor growth, consumption of the fish oil HFD uncoupled obesity from increased mammary tumor growth and exhibited a decrease in protumor macrophages. Compared with fatty acid (FA) components in both HFDs, n-3 FA rich in the fish oil HFD induced significant production of reactive oxygen species (ROS) and macrophage death. Moreover, A-FABP expression in the protumor macrophages facilitated intracellular transportation of n-3 FA and oxidation of mitochondrial FA. A-FABP deficiency diminished n-3 FA–mediated ROS production and macrophage death in vitro and in vivo . Together, our results demonstrate a novel mechanism by which n-3 FA induce ROS-mediated protumor macrophage death in an A-FABP–dependent manner. Significance: This study provides mechanistic insight into dietary supplementation with fish oil for breast cancer prevention and advances a new concept that not all HFDs leading to obesity are tumorigenic. Graphical Abstract: .

中文翻译：

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鱼油高脂饮食的摄取通过诱导巨噬细胞中的活性氧来消除肥胖和乳腺肿瘤的生长。

肥胖与多种类型癌症的风险增加相关，并且可以由来自不同脂肪来源的各种高脂饮食（HFD）诱发。尚不清楚不同HFD中的脂肪酸组成是否会影响与肥胖相关的肿瘤的发展。在这里，我们报告食用可可脂或鱼油HFD会在小鼠模型中引起类似的肥胖。虽然可可脂HFD诱导的肥胖症与乳腺肿瘤的加速生长相关，但食用鱼油HFD却使肥胖症与乳腺肿瘤的生长增加没有关系，并显示出巨噬细胞的减少。与两种HFD中的脂肪酸（FA）成分相比，富含鱼油HFD的n-3 FA引起大量的活性氧（ROS）产生和巨噬细胞死亡。此外，肿瘤巨噬细胞中的A-FABP表达促进n-3 FA的细胞内运输和线粒体FA的氧化。A-FABP缺乏可减少体内外n-3 FA介导的ROS产生和巨噬细胞死亡。在一起，我们的结果证明了一种新的机制，其中n-3 FA以A-FABP依赖性方式诱导ROS介导的ROS巨噬细胞死亡。启示：这项研究提供了膳食补充鱼油预防乳腺癌的机制，并提出了一个新概念，即并非所有导致肥胖的HFD都具有致瘤性。图形概要：我们的结果证明了一种新的机制，其中n-3 FA以依赖A-FABP的方式诱导ROS介导的肿瘤巨噬细胞死亡。启示：这项研究提供了膳食补充鱼油预防乳腺癌的机制，并提出了一个新概念，即并非所有导致肥胖的HFD都具有致瘤性。图形概要：我们的结果证明了一种新的机制，其中n-3 FA以依赖A-FABP的方式诱导ROS介导的肿瘤巨噬细胞死亡。启示：这项研究提供了膳食补充鱼油预防乳腺癌的机制，并提出了一个新概念，即并非所有导致肥胖的HFD都具有致瘤性。图形概要：。