Much less is known about the origin, phenotypes and function of macrophages in human AT. Human ATM have been described to be less polarized, which may be considered as an index of chronic inflammation. Indeed, hATM expressed both pro- and antiinflammatory markers and the lymphatic vessel endothelial hyaluronan receptor 1, a specific marker of macrophages involved in tumor growth and wound healing, as well as in mouse AT angiogenesis. In addition, hATM-conditioned media stimulated AT-derived endothelial cell migration and organization in capillary-like structures. Interestingly, hATM also expressed and secreted matrix metalloproteinase 9. MMP-9 is not only a key enzyme involved in angiogenesis but is also responsible for the proteolytic activation of latent transforming growth factor beta, itself implicated in the development of fibrosis. Indeed, TGFb is known to induce the appearance of extracellular matrix-secreting myofibroblasts, via the enhanced expression of several developmental transcription factors, including Snail and Slug. In obese mice models, Strissel et al. reported, a widespread deposition of collagen that coincided with adipocyte death and macrophage infiltration. More recently, data in humans confirmed that fat mass extension was correlated with collagen deposition and Bemegride fibrosis within AT, leading to systemic metabolic disturbances. The number of ATM and their phenotype and location within the AT appeared to be closely related to the foci of fibrosis. Interestingly, large scale transcriptomic analyses of AT from obese humans, together with immunohistochemical analysis and in vitro approaches, have shown that inflammatory Begacestat monocyte-derived macrophages induced phenotypic alterations of human AT progenitor cells that resulted in excessive synthesis of extracellular matrix components. Furthermore, we and others have shown that factors secreted by hATM inhibited the adipogenesis of human AT progenitor cells either directly or through the enhanced expression of a TGFb family member, INBHA/activinA. The fate of these AT progenitor cells arrested by hATM-derived factors remains to be established. The present study was undertaken to 1) investigate the influence of adiposity, AT location and its microenvironment on the phenotype of native hATM in terms of angiogenic and matrix remodeling/pro-fibrotic factors and 2) analyze the phenotype of native human AT progenitor cells arrested by macrophage-derived factors. Extensive AT growth has been recently associated with increased fibrosis in rodents as well as in humans. We previously showed that ATM from the ScAT of lean and overweight subjects exhibited a phenotype characterized by the specific expression of MMP-9 and pro-angiogenic properties. The present study extends these data to ATM from obese individuals in agreement with recent literature. Moreover, based on gene expression profiles determined on native ATM, we could distinguish two main phenotypes related to angiogenesis in OmAT and to matrix remodeling/fibrosis in ScAT. The MMPs, and more particularly MMP-9, play a key role in the proteolytic activation of latent TGFb1, itself involved in extracellular matrix homeostasis and fibrosis. Secretions from mature subcutaneous adipocytes favored the appearance of a matrix remodeling/fibrosis-related phenotype in ScATM, as shown by the increased expression of TGFb1 and MMP-9. Unexpectedly, MMP-2 level was decreased in this condition. Although MMP-2 and 9 are functionally related, the composition of their promoter is quite different leading to specific gene regulation.