Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.

中文翻译：

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脂肪细胞外囊泡携带酶和脂肪酸，刺激肿瘤细胞中的线粒体代谢和重塑。

细胞外囊泡是脂肪细胞通讯中新兴的关键角色。值得注意的是，脂肪细胞脱落的小细胞外囊泡会刺激黑色素瘤细胞中的脂肪酸氧化和迁移，肥胖症的这些作用会增强。然而，所涉及的囊泡演员和细胞过程仍然未知。在这里，我们阐明了将脂肪细胞胞外小泡与代谢重构和细胞迁移联系起来的机制。我们显示脂肪细胞囊泡通过提供酶和底物刺激黑色素瘤脂肪酸氧化。在肥胖症中，细胞外囊泡的增强作用取决于增加的脂肪酸运输，而不是与脂肪酸氧化相关的酶。存储在癌细胞脂质滴中的这些脂肪酸在通过脂肪吞噬释放时驱动脂肪酸氧化。线粒体活性的这种增加将线粒体重新分配到迁移细胞的膜突起上，这对于在脂肪细胞囊泡存在下增加细胞迁移是必需的。我们的结果提供了关键的见解，了解细胞外囊泡在脂肪细胞和与肥胖特别相关的肿瘤之间发生的代谢合作中的作用。