title: Identification of an adipogenic niche for adipose tissue remodeling and restoration.
abstract: 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.
authors.affiliation: Center for Integrative and Metabolic Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Anelia P
authors.initials: AP
authors.lastname: Petkova
authors.forename: James G
authors.initials: JG
authors.lastname: Granneman
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000166:cytology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004149:Dioxoles; D018960:Hyaluronan Receptors; D022702:Receptors, Adrenergic, beta-3; C506896:Spp1 protein, mouse; D053495:Osteopontin; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D020796:Receptor, Platelet-Derived Growth Factor alpha