Lv Yibing, Zheng Yidan, Su Shanshan, Xiao Junyi, Yang Jie, Xiong Lingyun, Guo Yanyan, Zhou Xiaoqi, Guo Nengqiang, Lei Ping
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Medical Genetic Institute of Henan Province, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Lipid Res. 2025 Jan;66(1):100720. doi: 10.1016/j.jlr.2024.100720. Epub 2024 Dec 5.
The role of the monocyte marker CD14 in the regulation of obesity is increasingly recognized. Our observations indicated that Cd14 mice exhibited a leaner body shape compared to their wild-type (WT) counterparts. And the loss of CD14 alleviated high-fat diet-induced obesity in mice. In human subjects, CD14 level was tested to be positively correlated with overweight and obesity. However, the relationship between CD14 and the development of obesity remains only partially understood. To investigate the underlying mechanisms, adipose tissues (ATs) from Cd14 and WT mice were subjected to deep RNA sequencing. Gene Ontology enrichment analysis revealed a significant enhancement of angiogenesis-related function in the Cd14 epididymal adipose tissues compared to WT counterpart, which was accompanied by an upregulation of Cd301b. Subsequent assays confirmed the enhanced angiogenesis and more accumulation of CD301b macrophages in Cd14 epididymal adipose tissues. Because Igf1 expression has been suggested to be associated with Cd301b expression through pseudotime analysis, we found it was insulin-like growth factor 1 secreted from Cd14 macrophages that mediated the angiogenesis enhancement. Collectively, our findings indicate that CD14 deficiency increased the accumulation of CD14CD301b macrophages in ATs, which may serve as a proangiogenic marker, providing novel insights into the relationship between CD14 and obesity development.
单核细胞标志物CD14在肥胖调节中的作用日益受到认可。我们的观察结果表明，与野生型（WT）对照相比，Cd14基因敲除小鼠的体型更瘦。而且CD14的缺失减轻了小鼠高脂饮食诱导的肥胖。在人类受试者中，检测到CD14水平与超重和肥胖呈正相关。然而，CD14与肥胖发生之间的关系仍仅部分为人所知。为了研究潜在机制，对Cd14基因敲除小鼠和WT小鼠的脂肪组织（AT）进行了深度RNA测序。基因本体富集分析显示，与WT对照相比，Cd14基因敲除小鼠附睾脂肪组织中血管生成相关功能显著增强，同时Cd301b上调。随后的实验证实了Cd14基因敲除小鼠附睾脂肪组织中血管生成增强以及CD301b巨噬细胞的更多积累。由于通过伪时间分析表明Igf1表达与Cd301b表达相关，我们发现是Cd14巨噬细胞分泌的胰岛素样生长因子1介导了血管生成增强。总体而言，我们的研究结果表明，CD14缺乏增加了AT中CD14+CD301b巨噬细胞的积累，CD301b巨噬细胞可能作为促血管生成标志物，为CD14与肥胖发生之间的关系提供了新的见解。
