Identification of key genes and pathways revealing the central regulatory mechanism of brain-derived glucagon-like peptide-1 on obesity using bioinformatics analysis.

Objective: Central glucagon-like peptide-1 (GLP-1) is a target in treating obesity due to its effect on suppressing appetite, but the possible downstream key genes that GLP-1 regulated have not been studied in depth. This study intends to screen out the downstream feeding regulation genes of central GLP-1 neurons through bioinformatics analysis and verify them by chemical genetics, which may provide insights for future research. Materials and methods: GSE135862 genetic expression profiles were extracted from the Gene Expression Omnibus (GEO) database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were carried out. STRING database and Cytoscape software were used to map the protein-protein interaction (PPI) network of the differentially expressed genes (DEGs). After bioinformatics analysis, we applied chemogenetic methods to modulate the activities of GLP-1 neurons in the nucleus tractus solitarius (NTS) and observed the alterations of screened differential genes and their protein expressions in the hypothalamus under different excitatory conditions of GLP-1 neurons. Results: A total of 49 DEGs were discovered, including 38 downregulated genes and 11 upregulated genes. The two genes with the highest expression scores were Conclusion: Our data showed that GLP-1 could modulate the protein expression of Bgn and Mapkapk3. Our findings elucidated the regulatory network in GLP-1 to obesity and might provide a novel diagnostic and therapeutic target for obesity.