College of Sport and Health, Shandong Sport University, Jinan, Shandong Province 250102, China.
College of Sport and Health, Shandong Sport University, Jinan, Shandong Province 250102, China.
Int Immunopharmacol. 2024 Nov 15;141:112962. doi: 10.1016/j.intimp.2024.112962. Epub 2024 Aug 27.
Macrophages in obese adipose tissue have been shown to damage nerve fibers, however, the mechanism underlying how macrophages cause glial cell damage remains unknown. This study aimed to characterize the mechanism by which macrophages induce apoptosis in glial cell during obesity formation in mice by single-nucleus RNA sequencing (snRNA-seq). Cells obtained from paraepididymal adipose tissue in obese mice underwent snRNA-seq. Eighteen different clusters were identified, and 12 cell types were annotated, including glial cells, macrophages, and fibroblasts. There was a negative correlation between the number of glial cells and macrophages in mouse adipose tissue during the formation of obesity. The pro-apoptotic factor PHLPP1 was identified in GO Terms. The interaction between adipose tissue glial cells and macrophages was revealed via in-depth analysis, and the cell-cell communication mechanism between the TNF-α and NF-KB/PHLPP1 axes was perfected. Apoptosis of glial cell by upregulation of TNF-α via obesity-derived macrophages and activation of the NF-κB/PHLPP1 axis. We further revealed how macrophages induce apoptosis in glial cells during obesity formation, as well as different changes in the two cell populations. This study provides valuable resources and foundations for understanding the mechanistic effects of macrophages and glial cells during obesity formation, as well as diseases and potential interventions.
肥胖脂肪组织中的巨噬细胞已被证明会损伤神经纤维，然而，巨噬细胞导致神经胶质细胞损伤的机制尚不清楚。本研究旨在通过单细胞 RNA 测序（snRNA-seq）来描述巨噬细胞在肥胖形成过程中诱导神经胶质细胞凋亡的机制。从肥胖小鼠附睾旁脂肪组织中获取的细胞进行 snRNA-seq 分析。鉴定出 18 个不同的簇，注释了 12 种细胞类型，包括神经胶质细胞、巨噬细胞和成纤维细胞。在肥胖形成过程中，小鼠脂肪组织中神经胶质细胞和巨噬细胞的数量呈负相关。GO 术语中鉴定出促凋亡因子 PHLPP1。通过深入分析揭示了脂肪组织神经胶质细胞和巨噬细胞之间的相互作用，完善了 TNF-α 和 NF-KB/PHLPP1 轴之间的细胞间通讯机制。肥胖衍生的巨噬细胞通过上调 TNF-α 诱导神经胶质细胞凋亡，并激活 NF-κB/PHLPP1 轴。我们进一步揭示了巨噬细胞如何在肥胖形成过程中诱导神经胶质细胞凋亡，以及这两个细胞群体的不同变化。本研究为理解肥胖形成过程中巨噬细胞和神经胶质细胞的机制作用以及相关疾病和潜在干预措施提供了有价值的资源和基础。
