Differentially Expressed Genes and Enriched Signaling Pathways in the Adipose Tissue of Obese People

Zhenhua Lu; Lingbing Meng; Zhen Sun; Xiaolei Shi; Weiwei Shao; Yangyang Zheng; Xinglei Yao; Jinghai Song

doi:10.3389/fgene.2021.620740

Differentially Expressed Genes and Enriched Signaling Pathways in the Adipose Tissue of Obese People

Front Genet. 2021 May 19:12:620740. doi: 10.3389/fgene.2021.620740. eCollection 2021.

Authors

Zhenhua Lu¹, Lingbing Meng², Zhen Sun¹, Xiaolei Shi¹, Weiwei Shao¹, Yangyang Zheng¹, Xinglei Yao^{3

4}, Jinghai Song¹

Affiliations

¹ Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
² Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing, China.
³ Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
⁴ College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China.

Abstract

As the prevalence of obesity increases, so does the occurrence of obesity-related complications, such as cardiovascular and cerebrovascular diseases, diabetes, and some cancers. Increased adipose tissue is the main cause of harm in obesity. To better understand obesity and its related complications, we analyzed the mRNA expression profiles of adipose tissues from 126 patients with obesity and 275 non-obese controls. Using an integrated bioinformatics method, we explored the functions of 113 differentially expressed genes (DEGs) between them. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses revealed that upregulated DEGs were enriched in immune cell chemotaxis, complement-related cascade activation, and various inflammatory signaling pathways, while downregulated DEGs enriched in nutrient metabolism. The CIBERSORT algorithm indicated that an increase in macrophages may be the main cause of adipose tissue inflammation, while decreased γδ T cells reduce sympathetic action, leading to dysregulation of adipocyte thermogenesis. A protein-protein interaction network was constructed using the STRING database, and the top 10 hub genes were identified using the cytoHubba plug-in in Cytoscape. All were confirmed to be obesity-related using a separate dataset. In addition, we identified chemicals related to these hub genes that may contribute to obesity. In conclusion, we have successfully identified several hub genes in the development of obesity, which provide insights into the possible mechanisms controlling obesity and its related complications, as well as potential biomarkers and therapeutic targets for further research.

Keywords: adipose tissue; bioinformatics; inflammation; mechanism; obesity.