Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells.

Publication date: Jan 10, 2020

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.

Clement, E., , Lazar, Attan’e, C., Carri’e, L., Dauvillier, S., Ducoux-Petit, M., Esteve, D., Menneteau, T., Moutahir, M., Le Gonidec, S., Dalle, S., Valet, P., Burlet-Schiltz, O., Muller, C., and Nieto, L. Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. 25432. 2020 EMBO J.

Concepts Keywords
Adipocyte Tumor
Adipocytes Enzymes substrates obesity
EMBO Melanoma
Extracellular Vesicles Branches of biology
Fatty Acid Metabolism
Fatty Acids Fatty acids
Lipid Adipocyte
Melanoma Beta oxidation
Membrane Lipid droplet
Metabolism Vesicle
Mitochondria Insulin
Mitochondrial Adipocyte protein 2
Obesity Fatty acid metabolism
Oxidation
Substrates
Tumor
Vesicles
Vesicular

Semantics

Type Source Name
pathway REACTOME Fatty acids
disease MESH tumor
disease MESH melanoma
pathway KEGG Melanoma
disease MESH obesity

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