Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Metab. 2012 Feb 8;15(2):222-9. doi: 10.1016/j.cmet.2012.01.008.
Adipose tissue expansion involves the enlargement of existing adipocytes, the formation of new cells from committed preadipocytes, and the coordinated development of the tissue vascular network. Here we find that murine endothelial cells (ECs) of classic white and brown fat depots share ultrastructural characteristics with pericytes, which are pluripotent and can potentially give rise to preadipocytes. Lineage tracing experiments using the VE-cadherin promoter reveal localization of reporter genes in ECs and also in preadipocytes and adipocytes of white and brown fat depots. Furthermore, capillary sprouts from human adipose tissue, which have predominantly EC characteristics, are found to express Zfp423, a recently identified marker of preadipocyte determination. In response to PPARγ activation, endothelial characteristics of sprouting cells are progressively lost, and cells form structurally and biochemically defined adipocytes. Together these data support an endothelial origin of murine and human adipocytes, suggesting a model for how adipogenesis and angiogenesis are coordinated during adipose tissue expansion.
脂肪组织扩张涉及现有脂肪细胞的增大、由定向前脂肪细胞形成新细胞,以及组织血管网络的协调发育。在这里,我们发现经典白色和棕色脂肪库的鼠类内皮细胞 (EC) 具有与周细胞相似的超微结构特征,周细胞是多能的,并且可以潜在地产生前脂肪细胞。使用 VE-cadherin 启动子的谱系追踪实验表明,报告基因定位于 EC 以及白色和棕色脂肪库的前脂肪细胞和脂肪细胞中。此外,从人脂肪组织中发现的具有主要 EC 特征的毛细血管芽殖被发现表达 Zfp423,这是最近确定的前脂肪细胞决定的标志物。响应 PPARγ 激活,芽殖细胞的内皮特征逐渐丧失,并且细胞形成结构和生物化学定义明确的脂肪细胞。这些数据共同支持鼠类和人类脂肪细胞的内皮起源,提示了在脂肪组织扩张过程中如何协调脂肪生成和血管生成的模型。