Zhang Fu-Rong, Lu Xuan, Li Jia-Li, Li Yu-Xin, Pang Wei-Wei, Wang Ning, Liu Kun, Zhang Qian-Qian, Deng Yun, Zeng Qin, Qu Xiao-Chao, Chen Xiang-Ding, Deng Hong-Wen, Tan Li-Jun
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Zebrafish Genetics Laboratory, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
Genes (Basel). 2025 Jun 30;16(7):783. doi: 10.3390/genes16070783.
Obesity is characterized by a chronic state of low-grade inflammation. Investigating immune-critical genes and their biological functions in the adipose tissue of postmenopausal obese women is crucial for elucidating the underlying mechanisms of immune dysregulation associated with obesity. In this study, microarray (GSE151839) and single-cell RNA-seq (GSE176171) datasets were obtained from the Gene Expression Omnibus (GEO). For microarray data analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction network (PPI) analysis, and immune infiltration analysis (ssGSEA) were employed to identify obesity-related immune-critical genes. Subsequently, the candidate genes were validated using scRNA-seq data to explore their expression patterns at the single-cell level. Finally, the expression levels of these immune-critical genes were experimentally verified in adipose tissue from obese and control zebrafish models using RT-qPCR. Analysis of microarray data through WGCNA, PPI and ssGSEA identified 16 obesity-related immune-critical genes, including , , , , , , , , , , , , , , , and . Differential expression of , and was confirmed in scRNA-seq data, with and showing distinct expression patterns in natural killer (NK) cells. Furthermore, RT-qPCR analysis revealed upregulation of and in adipose tissue of obese zebrafish compared to lean controls. This study identifies , and as key immune hub genes in the adipose tissue of postmenopausal obese women, with NK cells playing a significant role in adipose tissue inflammation through the expression of these genes. These findings provide novel insights into potential therapeutic targets for the prevention and treatment of obesity in postmenopausal women.
肥胖的特征是慢性低度炎症状态。研究绝经后肥胖女性脂肪组织中免疫关键基因及其生物学功能，对于阐明与肥胖相关的免疫失调潜在机制至关重要。在本研究中，从基因表达综合数据库（GEO）获取了微阵列（GSE151839）和单细胞RNA测序（GSE176171）数据集。对于微阵列数据分析，采用加权基因共表达网络分析（WGCNA）、蛋白质-蛋白质相互作用网络（PPI）分析和免疫浸润分析（ssGSEA）来识别肥胖相关的免疫关键基因。随后，使用单细胞RNA测序数据验证候选基因，以探索它们在单细胞水平的表达模式。最后，使用RT-qPCR在肥胖和对照斑马鱼模型的脂肪组织中通过实验验证这些免疫关键基因的表达水平。通过WGCNA、PPI和ssGSEA对微阵列数据进行分析，确定了16个肥胖相关的免疫关键基因，包括 、 、 、 、 、 、 、 、 、 、 、 、 、 、 和 。在单细胞RNA测序数据中证实了 、 和 的差异表达，其中 和 在自然杀伤（NK）细胞中表现出不同的表达模式。此外，RT-qPCR分析显示，与瘦对照组相比，肥胖斑马鱼脂肪组织中 和 上调。本研究确定 、 和 是绝经后肥胖女性脂肪组织中的关键免疫枢纽基因，NK细胞通过这些基因的表达在脂肪组织炎症中发挥重要作用。这些发现为绝经后女性肥胖的预防和治疗提供了潜在治疗靶点的新见解。
