Li Fangyu, Li Rui, Deng Hongjun
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Rehabilitation Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pharmacol. 2025 Jan 24;16:1521416. doi: 10.3389/fphar.2025.1521416. eCollection 2025.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for type 2 diabetes mellitus (T2DM), and its early identification and intervention offer opportunities for reversing diabetes mellitus.
In this study, we identified biomarkers for the MASLD dataset (GSE33814, GSE48452) and the T2DM dataset (GSE76895 and GSE89120) by bioinformatics analysis. Next, we constructed weighted gene co-expression network (WGCNA) for disease module analysis to screen out shared genes strongly associated with diseases. We also analyzed the enriched pathways of shared genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Next, hub gene validation was performed using the least absolute shrinkage and selection operator (LASSO) and receiver operating characteristic (ROC) curves. Finally, we used RT-qPCR, immunofluorescence, Western blotting and Elisa to validate hub gene expression in MASLD and T2DM mouse models.
This analysis identified 20 genes shared by MASLD and T2DM that were enriched in the bile secretion, phototransduction, cancer, carbohydrate digestion and absorption, cholesterol/glycerol metabolism, and retinol metabolism. The LASSO algorithm and ROC curve identified ( as the best diagnostic gene for MASLD and T2DM. Immunofluorescence and Western blot showed that RDH10 expression was reduced in the liver and pancreatic islets of MASLD and T2DM model mice. Similarly, serum levels of RDH10 were significantly lower in MASLD and T2DM model mice and humans than in controls.
Our study suggests that RDH10 is a common diagnostic marker for MASLD and T2DM and provides new research directions for the prevention and treatment of MASLD and T2DM.
代谢功能障碍相关脂肪性肝病（MASLD）是2型糖尿病（T2DM）的独立危险因素，其早期识别和干预为逆转糖尿病提供了机会。
在本研究中，我们通过生物信息学分析确定了MASLD数据集（GSE33814、GSE48452）和T2DM数据集（GSE76895和GSE89120）的生物标志物。接下来，我们构建加权基因共表达网络（WGCNA）进行疾病模块分析，以筛选出与疾病密切相关的共享基因。我们还使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析共享基因的富集通路。接下来，使用最小绝对收缩和选择算子（LASSO）和受试者工作特征（ROC）曲线进行枢纽基因验证。最后，我们使用RT-qPCR、免疫荧光、蛋白质免疫印迹和酶联免疫吸附测定（ELISA）来验证枢纽基因在MASLD和T2DM小鼠模型中的表达。
该分析确定了MASLD和T2DM共有的20个基因，这些基因在胆汁分泌、光转导、癌症、碳水化合物消化和吸收、胆固醇/甘油代谢以及视黄醇代谢中富集。LASSO算法和ROC曲线确定（此处原文缺失具体基因名称）为MASLD和T2DM的最佳诊断基因。免疫荧光和蛋白质免疫印迹显示，MASLD和T2DM模型小鼠的肝脏和胰岛中RDH10表达降低。同样，MASLD和T2DM模型小鼠及人类血清中的RDH10水平明显低于对照组。
我们的研究表明，RDH10是MASLD和T2DM的常见诊断标志物，为MASLD和T2DM的预防和治疗提供了新的研究方向。
