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Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades. Obesity involvement in melanoma aetiology has been recognized, but the implicated mechanisms remain unclear. In the present study, we address this relationship and investigate the influence of adipocytes secretome on B16\u2010F10 and MeWo melanoma cell lines. Using the 3T3\u2010L1 adipocyte cell line, as well as ex vivo subcutaneous (SAT) and visceral (VAT) adipose tissue conditioned medium, we were able to show that adipocyte\u2010released factors play a dual role in increasing melanoma cell overall survival, both by enhancing proliferation and decreasing apoptosis. B16\u2010F10 cell migration and cell\u2013cell and cell\u2013matrix adhesion capacity were predominantly enhanced in the presence of SAT and VAT released factors. Melanocytes morphology and melanin content were also altered by exposure to adipocyte conditioned medium disclosing a more dedifferentiated phenotype of melanocytes. In addition, exposure to adipocyte\u2010secreted molecules induced melanocytes to rearrange, on 3D cultures, into vessel\u2010like structures, and generate characteristic vasculogenic mimicry patterns. These findings are corroborated by the released factors profile of 3T3\u2010L1, SAT, and VAT assessed by microarrays, and led us to highlight the mechanisms by which adipose secretome from sub\u2010cutaneous or visceral depots promote melanoma progression. J. Cell. 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