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Enhanced expression of the aggrecanase ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) has been observed in adipose tissue (AT) of obese rodents. Here, we have investigated the role of ADAMTS5 in adipogenesis, AT expansion and associated angiogenesis. In vitro differentiation of precursor cells into mature adipocytes was studied using murine embryonic fibroblasts (MEF) derived from wild-type (Adamts5 ^+/+) and ADAMTS5 deficient (Adamts5 ^-/-) mice, or 3T3-F442A preadipocytes with stable gene silencing of Adamts5. De novo adipogenesis was monitored by injection of 3T3-F442A cells with or without Adamts5 knockdown in Nude mice. Furthermore, Adamts5^+/+ and Adamts5^/- mice were kept on a high-fat diet (HFD) to monitor AT development. Adamts5^-/- MEF, as well as 3T3-F442A preadipocytes with Adamts5 knockdown, showed significantly reduced …