Nutritional 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.
Bibliographical noteFunding Information:
We thank Drs. W. Richardson and D. McTigue for providing Pdgfra -CreER mice and Dr. T. Leff, Dr. R. MacKenzie, and members of CIMER for discussions. This study was supported by NIH grants (RO1DK62292 and RO1DK76629) to J.G.G. E.P.M. was supported by a Doctoral Research Award from CIHR. The Microscopy, Imaging and Cytometry Resources Core is supported, in part, by NIH Center grant P30CA22453.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology