New research has identified a novel mode of communication between adipocytes and cancer cells that regulates tumour aggressiveness. Adipocyte exosomes (ad-exos) purified from conditioned medium of 3T3-F442A mature adipocytes increased melanoma cell migration and invasion in vitro. Analysis of the protein cargo of these ad-exos by mass spectrometry revealed the majority of proteins to be involved in lipid metabolism, specifically fatty acid oxidation (FAO). Crucially, inhibition of this pathway blocked the pro-migratory effect of ad-exos on melanoma cells, highlighting the importance of FAO in tumour progression. Shedding of ad-exos and their effect on FAO-dependent melanoma cell migration were also greater in obese mice and humans than in lean controls. The findings could explain why patients with obesity and melanoma have a poor prognosis and lead to new cancer treatments involving FAO inhibitors.