Endocrine Abstracts

Introduction

Epidemiological studies have suggested that obesity during childhood increases the risk of developing metabolic comorbidities, such as type 2 diabetes, later in life. Childhood obesity is a complex disease whose molecular mechanisms are not completely elucidated. However, studies have demonstrated that approximately 65% of the variation associated with obesity is due to genetic factors. In this context, a system biology approach could contribute to the scientific knowledge regarding genetic factors related to childhood obesity onset.

Aim

To identify molecular mechanisms involved in childhood obesity by implementing a system biology approach.

Methods

Experimentally validated and computationally predicted genes related to Pediatric Obesity (C2362324) were downloaded from the DisGeNET v7.0 database. The protein–protein interaction (PPI) network was constructed using the STRING v11.0 database and analyzed using Cytoscape v3.8.2. The relevance of each node for the network structure and functionality was assessed using the degree and betweenness algorithms to define the hub-bottleneck genes. Functional and pathway enrichment analyses were performed based on Gene Ontology (GO) terms and KEGG Pathways.

Results

The search on the DisGeNET database retrieved 191 childhood obesity-related genes. After the PPI network analysis, 12 hub-bottleneck genes were identified: INS, LEP, STAT3, POMC, ALB, TNF, BDNF, CAT, GCG, PPARG, VEGFA, and ADIPOQ. These hub-bottleneck genes are involved in several biological processes, including regulation of gluconeogenesis, lipid export from cells, and response to vitamin E. Regarding KEGG pathways, these genes were enriched in adipocytokine signaling, insulin resistance, longevity regulation, thermogenesis, and cytokine signaling pathways.

Conclusion

Our approach identified 12 hub-bottleneck genes that are highly connected and probably have a key role in childhood obesity. Moreover, functional enrichment analyses demonstrated that they are enriched in several biological processes and pathways related to the underlying molecular mechanisms of obesity. These findings provide a more comprehensive information regarding genetic and molecular factors behind childhood obesity pathogenesis.