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.

中文翻译：

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三维脂肪组织成像揭示了米色脂肪生物发生和PRDM16依赖的交感神经突密度中的区域差异。

尽管越来越多地描述了控制米色脂肪细胞发育和表型的细胞内源性途径，但关于米色脂肪细胞如何与脂肪中其他细胞类型相互作用的信息知之甚少。在这里，我们介绍了一种用于脂肪的全组织清除方法，该方法可以进行免疫标记和三维结构化分析，包括产热脂肪细胞和交感神经。我们发现皮下和内脏贮库之间的组织结构和交感神经支配有显着差异。皮下脂肪显示出UCP1 ⁺定位的米色脂肪生物发生中的显着区域差异米色脂肪细胞到具有密集交感神经突的区域。我们目前的证据表明，交感神经投射的密度取决于脂肪细胞中的PRDM16，从而提供了另一种潜在的机制，该机制潜在于PRDM16介导的代谢益处。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，并揭示了脂肪细胞对交感神经系统进行以前未曾描述的调节方式。