Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density
Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density
复制标题
DOI：
10.1016/j.cmet.2017.12.011
复制
发表时间：
2018-01-09
期刊：
影响因子：
29
通讯作者：
Cohen, Paul
中科院分区：
文献类型：
--
作者：
Chi, Jingyi;Wu, Zhuhao;Cohen, Paul
虽然越来越多地描述了米色脂肪细胞发育和表型的细胞内在途径，但对米色脂肪细胞如何与脂肪中的其他细胞类型相互作用知之甚少。在这里，我们介绍了一种脂肪的全组织清除方法，该方法允许对包括产热脂肪细胞和交感神经支配在内的结构进行免疫标记和三维分析。我们发现，皮下和内脏贮库的组织结构和交感神经支配有显着差异。皮下脂肪显示米色脂肪生物发生的显著区域差异，UCP1（+）米色脂肪细胞定位于交感神经突起密集的区域。我们提出的证据表明，交感神经投射的密度依赖于脂肪细胞中的PRDM16，提供了另一种潜在的机制，潜在的代谢益处由PRDM16介导。这种强大的成像工具突出了米色脂肪生物发生过程中组织成分的相互作用，并揭示了以前未描述的脂肪细胞对交感神经系统的调节模式。
While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1(+) beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes.