Adipogenesis in obesity requires close interplay between differentiating adipocytes, strontal cells, and blood vessels
Adipogenesis in obesity requires close interplay between differentiating adipocytes, strontal cells, and blood vessels
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DOI：
10.2337/db06-1749
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发表时间：
2007-06-01
期刊：
影响因子：
7.7
通讯作者：
Sugiura, Seiryo
中科院分区：
文献类型：
--
作者：
Nishimura, Satoshi;Manabe, Ichiro;Sugiura, Seiryo
肥胖症-肥胖症中脂肪组织质量的扩张涉及脂肪细胞的增生和肥大。然而，人们对脂肪细胞、脂肪细胞前体、血管，研究设计和方法-我们已经开发了一种基于共聚焦显微镜的完整活脂肪组织三维可视化方法，使我们能够同时评估db/db小鼠的血管生成和脂肪生成。（我们将其命名为成脂/血管生成细胞簇），其包含多种细胞类型，包括表达CD 34和CD 68并结合凝集素的内皮细胞和基质细胞。血管形成和脂肪形成之间存在密切的空间和时间相关性，并且新血管从预先存在的脉管系统中发芽与脂肪细胞分化相耦合。CD 34（+）CD 68（+）凝集素结合细胞与CD 34（-）CD 68（+）巨噬细胞明显不同，后者散在分布于间质中，不结合凝集素。脂肪生成/血管生成细胞簇可以在形态学和免疫化学上与在脂肪组织肥胖的晚期经常看到的冠状结构区分开。抗血管内皮生长因子（VEGF）抗体的施用不仅抑制血管生成，而且还抑制脂肪形成/血管生成细胞簇的形成，表明脂肪形成和血管生成的偶联对于肥胖症中脂肪细胞的分化是必不可少的，并且VEGF是该过程的关键介质。基质细胞和活的肥胖脂肪组织中的血管生成。
OBJECTIVE-The expansion of adipose tissue mass seen in obesity involves both hyperplasia and hypertrophy of adipocytes. However, little is known about how adipocytes, adipocyte precursors, blood vessels, and stromal cells interact with one another to achieve adipogenesis.RESEARCH DESIGN AND METHODS-We have developed a confocal microscopy-based method of three-dimensional visualization of intact living adipose tissue that enabled us to simultaneously evaluate angiogenesis and adipogenesis in db/db mice.RESULTS-We found that adipocyte differentiation takes place within cell clusters (which we designated adipogenic/angiogenic cell clusters) that contain multiple cell types, including endothelial cells and stromal cells that express CD34 and CD68 and bind lectin. There were close spatial and temporal interrelationships between blood vessel formation and adipogenesis, and the sprouting of new blood vessels from preexisting vasculature was coupled to adipocyte differentiation. CD34(+) CD68(+) lectin-binding cells could clearly be distinguished from CD34(-) CD68(+) macrophages, which were scattered in the stroma and did not bind lectin. Adipogenic/angiogenic cell clusters can morphologically and immunohistochemically be distinguished from crown-like structures frequently seen in the late stages of adipose tissue obesity. Administration of anti-vascular endothelial growth factor (VEGF) antibodies inhibited not only angiogenesis but also the formation of adipogenic/angiogenic cell clusters, indicating that the coupling of adipogenesis and angiogenesis is essential for differentiation of adipocytes in obesity and that VEGF is a key mediator of that process.CONCLUSIONS-Living tissue imaging techniques provide novel evidence of the dynamic interactions between differentiating adipocytes, stromal cells, and angiogenesis in living obese adipose tissue.