In Vivo Identification of Bipotential Adipocyte Progenitors Recruited by β3-Adrenoceptor Activation and High-Fat Feeding

SummaryNutritional and pharmacological stimuli can dramatically alter the cellular phenotypes in white adipose tissue (WAT). Utilizing genetic lineage tracing techniques, we demonstrate that brown adipocytes (BA) that are induced by β3-adrenergic receptor activation in abdominal WAT arise from the proliferation and differentiation of cells expressing platelet-derived growth factor receptor alpha (PDGFRα), CD34, and Sca-1 (PDGFRα+ cells). PDGFRα+ cells have a unique morphology in which extended processes contact multiple cells in the tissue microenvironment. Surprisingly, these cells also give rise to white adipocytes (WA) that can comprise up to 25% of total fat cells in abdominal fat pads following 8 weeks of high-fat feeding. Isolated PDGFRα+ cells differentiated into both BA and WA in vitro and generated WA after transplantation in vivo. The identification of PDGFRα+ cells as bipotential adipocyte progenitors will enable further investigation of mechanisms that promote therapeutic cellular remodeling in adult WAT.

► β 3AR activation induces differentiation of PDGFRα+ cells into brown adipocytes ► Isolated PDGFRα+ cells have adipogenic potential in vivo and in vitro ► PDGFRα+ cells contribute to adipocyte hyperplasia induced by high-fat diet ► PDGFRα+ cells appear to be adult stem cells involved in WAT remodeling