Identification of significant modules and hub genes involved in fasting using WGCNA

Abstract

Background: Dietary interventions are one of the most common health promotion tools. Regular intermittent fasting is thought to reduce body weight and ameliorate adverse cardiovascular disease factors significantly. However, there is growing evidence that fasting positively affects body composition and biochemical parameters, but very few studies related to its mechanisms. In this study, bioinformatics network analysis was performed to investigate the effects of fasting on adipose and muscle tissues and further explore the potential mechanisms and targets of action. Methods: We downloaded the adipose tissue and muscle tissue gene expression datasets before and after fasting from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted correlation network analysis (WGCNA) to identify key modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the differential genes in adipose tissue and muscle tissue-related modules, respectively. Then, we constructed protein-protein interaction (PPI) networks using the STRING database and detected the central genes in the networks. Results: Functional enrichment analysis showed that AMPK pathway and neurodegenerative disease-related pathways might be involved in the regulation of fasting in humans. PPI network construction indicated that the regulation of fasting in humans, both in adipose and muscle tissues, may be associated with two central genes, TXNIP and DLAT, and that this regulation is likely to act on human metabolism. Conclusion: Our work indicates that a total of 15 key genes, including TXNIP, DLAT, PDK4, DDIT3, and PFKFB3, may receive regulation by fasting interventions, especially TXNIP and DLAT are the basis of fasting mechanisms in adipose and muscle tissues. The pathways regulated by these key genes may provide new targets for further studies on the mechanism of fasting and the treatment of metabolic diseases.