Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Cell Metab. 2017 Oct 3;26(4):686-692.e3. doi: 10.1016/j.cmet.2017.08.016. Epub 2017 Sep 14.
Efferent signals from the central nervous system represent a key layer of regulation of white adipose tissue (WAT). However, the mechanism by which efferent neural signals control WAT metabolism remains to be better understood. Here, we exploit the volume fluorescence-imaging technique to visualize the neural arborizations in mouse inguinal WAT at single-fiber resolution. The imaging reveals a dense network of sympathetic arborizations that had been previously undetected by conventional methods, with sympathetic fibers being in close apposition to > 90% of adipocytes. We demonstrate that these sympathetic fibers originate from the celiac ganglia, which are activated by cold challenge. Sympathetic-specific deletion of TrkA receptor or pharmacologic ablation by 6-hydroxydopamine abolishes these intra-adipose arborizations and, as a result, cold-induced beiging of inguinal WAT. Furthermore, we find that local sympathetic arborizations function through beta-adrenergic receptors in this beiging process. These findings uncover an essential link connecting efferent neural signals with metabolism of individual adipocytes.
来自中枢神经系统的传出信号代表了白色脂肪组织（WAT）调节的关键层。然而，传出神经信号控制 WAT 代谢的机制仍有待进一步理解。在这里，我们利用体积荧光成像技术以单纤维分辨率可视化小鼠腹股沟 WAT 中的神经分支。成像揭示了以前用传统方法无法检测到的密集交感神经分支网络，其中交感神经纤维与超过 90%的脂肪细胞紧密相邻。我们证明这些交感神经纤维源自腹腔神经节，它们会被冷刺激激活。交感神经特异性 TrkA 受体缺失或 6-羟多巴胺药理学消融会消除这些脂肪内分支，从而导致腹股沟 WAT 的冷诱导米色化。此外，我们发现局部交感神经分支通过β-肾上腺素能受体在这个米色化过程中发挥作用。这些发现揭示了传出神经信号与单个脂肪细胞代谢之间的重要联系。
