Jin Shuoshuo, Huang Jinya, Chen Kuangyang, Wang Xuanchun
Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
Ann Transl Med. 2022 Oct;10(19):1052. doi: 10.21037/atm-22-1010.
Metabolic syndrome (MetS) refers to a cluster of metabolic disorders that are mainly caused by obesity. Skeletal muscle is a central component of systemic metabolism. However, the mechanism of skeletal muscle metabolic impairment in obesity remains unclear. This study aimed to identify key early biomarkers in skeletal muscle for the prevention and treatment of MetS in obesity.
The GSE85439 dataset was downloaded from the Gene Expression Omnibus database. Gene set enrichment and immune cell infiltration analyses were performed for genome-wide genes. Differentially expressed genes (DEGs) between obese and control mice were screened and subjected to functional enrichment analysis, and a protein-protein interaction network was constructed. The results of the bioinformatics analysis were confirmed by immunofluorescence and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
Enrichment analysis indicated that the genes expressed in obese mice were mainly associated with acute inflammatory response. Immune cell infiltration analysis of 190 DEGs with consistent trends showed that the numbers of mast cells (MCs) and active dendritic cells were significantly higher in obese mice than in control mice. Immunofluorescence analysis confirmed that the number of MCs present in the skeletal muscle was higher in obese mice than in control mice, although no difference was observed in the active dendritic cell count. Functional enrichment analysis showed that the DEGs were mainly associated with transcriptional regulation. In the clusters of the protein-protein interaction network, four acute-phase-response genes (, , , and ) were significantly correlated with transcription-regulating genes (, , and ); these seven genes were identified as hub genes. The qRT-PCR results showed that the expression levels of , , , and were significantly higher in obese mice than in control mice; however, those of , , and did not differ significantly between the two groups.
The skeletal muscle of obese mice exhibits elevated MC infiltration and increased , , , and expression. The identification of these biomarkers has increased our understanding of the potential functional mechanisms of skeletal muscle in obesity. These potential biomarkers may serve as targets for the prevention and treatment of MetS.
代谢综合征（MetS）指的是一组主要由肥胖引起的代谢紊乱。骨骼肌是全身代谢的核心组成部分。然而，肥胖状态下骨骼肌代谢受损的机制仍不清楚。本研究旨在识别骨骼肌中用于预防和治疗肥胖相关代谢综合征的关键早期生物标志物。
从基因表达综合数据库下载GSE85439数据集。对全基因组基因进行基因集富集和免疫细胞浸润分析。筛选肥胖小鼠和对照小鼠之间的差异表达基因（DEG）并进行功能富集分析，构建蛋白质-蛋白质相互作用网络。通过免疫荧光和实时定量逆转录-聚合酶链反应（qRT-PCR）对生物信息学分析结果进行验证。
富集分析表明，肥胖小鼠中表达的基因主要与急性炎症反应相关。对190个具有一致趋势的DEG进行免疫细胞浸润分析显示，肥胖小鼠中肥大细胞（MC）和活化树突状细胞的数量显著高于对照小鼠。免疫荧光分析证实，肥胖小鼠骨骼肌中MC的数量高于对照小鼠，尽管活化树突状细胞计数未观察到差异。功能富集分析表明，DEG主要与转录调控相关。在蛋白质-蛋白质相互作用网络的簇中，四个急性期反应基因（、、和）与转录调节基因（、和）显著相关；这七个基因被确定为枢纽基因。qRT-PCR结果显示，肥胖小鼠中、、和的表达水平显著高于对照小鼠；然而，两组之间、和的表达水平没有显著差异。
肥胖小鼠的骨骼肌表现出MC浸润增加以及、、和表达升高。这些生物标志物的识别增进了我们对肥胖状态下骨骼肌潜在功能机制的理解。这些潜在的生物标志物可能作为预防和治疗代谢综合征的靶点。
