Identification of an adipogenic niche for adipose tissue remodeling and restoration

Cell Metab. 2013 Sep 3;18(3):355-67. doi: 10.1016/j.cmet.2013.08.003.


The regulatory events guiding progenitor activation and differentiation in adult white adipose tissue are largely unknown. We report that induction of brown adipogenesis by β3-adrenergic receptor (ADRB3) activation involves the death of white adipocytes and their removal by M2-polarized macrophages. Recruited macrophages express high levels of osteopontin (OPN), which attracts a subpopulation of PDGFRα+ progenitors expressing CD44, a receptor for OPN. Preadipocyte proliferation is highly targeted to sites of adipocyte clearance and occurs almost exclusively in the PDGFRα+ CD44+ subpopulation. Knockout of OPN prevents formation of crown-like structures by ADRB3 activation and the recruitment, proliferation, and differentiation of preadipocytes. The recruitment and differentiation of PDGFRα+ progenitors are also observed following physical injury, during matrix-induced neogenesis, and in response to high-fat feeding. Each of these conditions recruits macrophages having a unique polarization signature, which may explain the timing of progenitor activation and the fate of these cells in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipogenesis*
  • Adipose Tissue, White / cytology
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Dioxoles / pharmacology
  • Hyaluronan Receptors / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteopontin / antagonists & inhibitors
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptors, Adrenergic, beta-3 / chemistry
  • Receptors, Adrenergic, beta-3 / metabolism
  • Up-Regulation / drug effects


  • Dioxoles
  • Hyaluronan Receptors
  • Receptors, Adrenergic, beta-3
  • Spp1 protein, mouse
  • Osteopontin
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
  • Receptor, Platelet-Derived Growth Factor alpha