Abstract
The molecular mechanisms underlying obesity-related cardiomyopathy (ORCM) progression involve multiple signaling pathways, and the pharmacological treatment for ORCM is still limited. Thus, it is necessary to explore new targets and develop novel therapies. Microarray analysis for gene expression profiles using different bioinformatics tools has been an effective strategy for identifying novel targets for various diseases. In this study, we aimed to explore the potential genes related to ORCM using the integrated bioinformatics analysis. The GSE18897 (whole blood expression profiling of obese diet-sensitive, obese diet-resistant, and lean human subjects) and GSE47022 (regular weight C57BL/6 and diet-induced obese C57BL/6 mice) were used for bioinformatics analysis. Weighted gene co-expression network analysis (WGCNA) of GSE18897 was employed to investigate gene modules that were strongly correlated with clinical phenotypes. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the co-expression genes. The expression levels of the hub genes were validated in the clinical samples. Yellow co-expression module of WGCNA in GSE18897 was found to be significantly related to the caloric restriction treatment. In addition, GO functional enrichment analysis and KEGG pathway analysis were performed on the co-expression genes in yellow co-expression module, which showed an association with oxygen transport and the porphyrins pathway. Overlap analysis of yellow co-expression module genes from GSE18897 andGSE47022 revealed six upregulated genes, and further experimental validation results showed that elongation of very-long-chain fatty acids protein 4 (ELOVL4), matrix metalloproteinase-8 (MMP-8), and interleukin-33 (IL-33) were upregulated in the peripheral blood from patients with ORCM compared to that in the controls. The bioinformatics analysis revealed that ELOVL4 expression levels are positively correlated with that of IL-33. Collectively, using WGCNA in combination with integrated bioinformatics analysis, the hub genes of ELVOL4 and IL-33 might serve as potential biomarkers for diagnosis and/or therapeutic targets for ORCM. The detailed roles of ELVOL4 and IL-33 in the pathophysiology of ORCM still require further investigation.
Highlights
The number of overweight and obese individuals has dramatically increased
The present study provides preliminary insights into the molecular mechanisms underlying the progression of obesity-related cardiomyopathy (ORCM)
The human datasets were used for constructing gene networks with Weighted gene co-expression network analysis (WGCNA), and the expression models were subjected to Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis
Summary
The number of overweight and obese individuals has dramatically increased. In China, more than 10% of the adult population is obese (He et al, 2017; Qasim et al, 2018; Wang and Ren, 2018). While in America, the prevalence of obesity among adults is about 39.6% (Hales et al, 2018). China is the most populous country with a total population of 1.4 billion compared to 0.32 billion in America (in 2018). The prevalence of obesity is much higher in America than in China, the obese population is comparable in these two countries. In 2014, China ranked first worldwide, with 43.2 million obese men and 46.4 million obese women (Collaboration, 2016)
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