RESUMO
BACKGROUND: Childhood obesity is triggered by a complex interplay of environmental, genetic, and epigenetic factors; however, the molecular mechanisms behind this disease are not completely elucidated. Thus, the aim of this study was to investigate molecular mechanisms involved in childhood obesity by implementing a systems biology approach. METHODS: Experimentally validated and computationally predicted genes related to childhood obesity were downloaded from DisGeNET database. A protein-protein interaction (PPI) network was constructed using the STRING database and analyzed at Cytoscape web-tool. Hub-bottleneck genes and functional clusters were identified through CytoHubba and MCODE plugins, respectively. Functional enrichment analyses were performed based on Gene Ontology terms and KEGG Pathways. RESULTS: The DisGeNET search retrieved 191 childhood obesity-related genes. The resulting PPI network contained 12 hub-bottleneck genes (INS, LEP, STAT3, POMC, ALB, TNF, BDNF, CAT, GCG, PPARG, VEGFA, and ADIPOQ) and 4 functional clusters, with cluster 1 showing the highest interaction score. Genes at this cluster were enriched at inflammation, carbohydrate, and lipid metabolism pathways. With exception of POMC, all hub-bottleneck genes were found in cluster 1, which contains highly connected genes that possibly play key roles in obesity-related pathways. CONCLUSIONS: Our systems biology approach revealed a set of highly interconnected genes associated with childhood obesity, providing comprehensive information regarding genetic and molecular factors involved in the pathogenesis of this disease.