Center for Integrative and Metabolic Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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.
指导成年白色脂肪组织祖细胞激活和分化的调控事件在很大程度上尚不清楚。我们报告称，β3-肾上腺素能受体（ADRB3）激活诱导棕色脂肪生成涉及白色脂肪细胞的死亡及其被 M2 极化的巨噬细胞清除。募集的巨噬细胞表达高水平的骨桥蛋白（OPN），吸引表达 OPN 受体 CD44 的亚群 PDGFRα+祖细胞。前脂肪细胞增殖高度靶向于脂肪细胞清除部位，几乎仅发生在 PDGFRα+CD44+亚群中。OPN 的敲除可防止 ADRB3 激活形成冠状结构，并防止前脂肪细胞的募集、增殖和分化。在物理损伤、基质诱导新生和高脂喂养期间，也观察到 PDGFRα+祖细胞的募集和分化。这些条件中的每一种都会募集具有独特极化特征的巨噬细胞，这可以解释祖细胞激活的时间以及这些细胞在体内的命运。
