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This Podcast features an interview with Brian Feldman, author of a Research Article that appears in the 25 October 2016 issue of Science Signaling, about a secreted protein that inhibits the expansion of fat tissue in response to high-fat diet or glucocorticoids. Endogenous glucocorticoids play many roles in normal physiology, including the reduction of inflammation. Synthetic glucocorticoids such as dexamethasone are commonly used to treat inflammatory conditions, but long-term usage or high doses of these drugs cause obesity. Using a combination of primary mouse and human adipocytes, mice, and human volunteers, Wong et al. found that both overfeeding and dexamethasone treatment affected the abundance of the secreted protease ADAMTS1 in adipose tissue. ADAMTS1 stimulated a signaling pathway that increased adipocyte proliferation but inhibited adipocyte differentiation. Thus, ADAMTS1 links both diet and glucocorticoids to the balance between adipocyte proliferation and differentiation.