The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells
The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells
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DOI：
10.13128/ijae-11985
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发表时间：
2012
影响因子：
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通讯作者：
A. Frontini;Khanh-Van Tran;O. Gealekman;M. C. Zingaretti;S. Corvera;S. Cinti
中科院分区：
文献类型：
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作者：
A. Frontini;Khanh-Van Tran;O. Gealekman;M. C. Zingaretti;S. Corvera;S. Cinti
脂肪组织扩张包括现有脂肪细胞的扩大、脂肪祖细胞的分化和支持血管网的发育。尽管一些数据表明脂肪祖细胞存在于脂肪组织的脉管系统中，但它们的身份并不完全清楚[1，2]。在这里，我们解决的假设，一个人口的脂肪细胞来源于内皮细胞（EC）谱系。为了突出脂肪细胞前体的特征，我们在开发小鼠WAT和BAT中进行了详细的形态学分析。此外，我们使用VE-Cadherin- Cre/R26 R小鼠模型来解决血管EC和脂肪细胞发育之间的关系。该谱系追踪模型允许鉴定在分化期间的任何点表达EC基因VE-钙粘蛋白的细胞。最后，我们分析了来自人类皮下脂肪组织的毛细血管芽，以评估形成这些结构的EC具有转化为脂肪细胞的能力的假设。强烈的脂肪形成的离散区域，我们指定的血管脂肪细胞胰岛的超微结构分析，揭示了罕见的内皮细胞周细胞的存在下，可以代表一个中间的发展步骤之间的EC和前脂肪细胞阶段。使用VE-钙粘蛋白启动子的谱系追踪实验揭示了报告基因在白色和棕色脂肪库的EC、前脂肪细胞和脂肪细胞中的表达。此外，发现来自人脂肪组织的毛细血管芽（其主要具有EC特征）表达Zfp 423，Zfp 423是最近鉴定的前脂肪细胞测定的标志物[3]。随着PPARγ的激活，内皮细胞逐渐丧失其结构和分子特征，形成结构和生化特征明确的脂肪细胞。我们报告了形态学和遗传学证据，即白色和棕色脂肪库中的脂肪细胞来源于显示内皮特征的细胞，这与其他研究人员发表的结果[4]以及我们实验室以前的工作[5]一致。
Adipose tissue expansion involves the enlargement of existing adipocytes, the differentiation of adipocyte progenitors, and the development of the supporting vascular network. Although some data suggest that the adipocyte progenitors reside in the vasculature of the adipose tissue, their identity is not completely clear [1,2]. Here we address the hypothesis that a population of adipocytes derives from an endothelial cell (EC) lineage. We performed a detailed morphological analysis in developing murine WAT and BAT in order to highlight the features of adipocyte precursors. In addition, we used the VE-Cadherin- Cre/R26R mouse model to address the relationship between vascular ECs and adipose cells development. This lineage tracing model allowed the identification of cells that express the EC gene VE-Cadherin at any point during differentiation. Finally, we analyzed capillary sprouts arising from human subcutaneous fat tissue to evaluate the hypothesis that ECs forming these structures possess the capacity to transform into adipocytes. Ultrastructural analysis of discrete areas of intense adipogenesis, that we designated vasculo-adipocytic islets, revealed the presence of rare endothelial-pericytic cells that could represent an intermediate developmental step between the EC and the preadipocyte stage. Lineage tracing experiments using the VE-cadherin promoter revealed the expression of reporter genes in ECs, preadipocytes and adipocytes in white and brown fat depots. Furthermore, capillary sprouts (which have predominantly EC characteristics) from human adipose tissue were found to express Zfp423, a recently identified marker of preadipocyte determination [3]. In response to PPARγ activation the ECs lost progressively their structural and molecular characteristics, and formed structurally and biochemically defined adipocytes. We report morphological and genetic evidence that adipocytes in white and brown fat depots originate from cells that display endothelial characteristics and this is in accordance with the results published by other researchers [4] and also with previous works performed in our lab [5].