Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach

Abstract

Childhood obesity carries an increased risk of metabolic complications, sleep disturbances, and cancer. Visceral adiposity is independently associated with inflammation and insulin resistance in obese children. However, the underlying pathogenic mechanisms are still unclear. We aimed to detect the gene expression pattern and its regulatory network in the visceral adipose tissue of obese pediatric individuals. Using differentially-expressed genes (DEGs) identified from two publicly available datasets, GSE9624 and GSE88837, we performed functional enrichment, protein–protein interaction, and network analyses to identify pathways, targeting transcription factors (TFs), microRNA (miRNA), and regulatory networks. There were 184 overlapping DEGs with six significant clusters and 19 candidate hub genes. Furthermore, 24 TFs targeted these hub genes. The genes were regulated by miR-16-5p, miR-124-3p, miR-103a-3p, and miR-107, the top miRNA, according to a maximum number of miRNA–mRNA interaction pairs. The miRNA were significantly enriched in several pathways, including lipid metabolism, immune response, vascular inflammation, and brain development, and were associated with prediabetes, diabetic nephropathy, depression, solid tumors, and multiple sclerosis. The genes and miRNA detected in this study involve pathways and diseases related to obesity and obesity-associated complications. The results emphasize the importance of the TGF-β signaling pathway and its regulatory molecules, the immune system, and the adipocytic apoptotic pathway in pediatric obesity. The networks associated with this condition and the molecular mechanisms through which the potential regulators contribute to pathogenesis are open to investigation.

Analyzing the Association of Visceral Adipose Tissue Growth Differentiation Factor-15 and MicroRNA in Type 2 Diabetes Mellitus

“… 33 The TGF-β signalling pathway has been implicated in childhood obesity in a recent in silico study. 34 Functional enrichment for miRNA also identified the regulation of phosphatase and tensin homolog (PTEN) as a highly significant pathway in REACTOME. PTEN has an established role in hyperglycaemia and in the pathogenesis of diabetic nephropathy through miRNA.…”

The Role of Molecular and Hormonal Factors in Obesity and the Effects of Physical Activity in Children

“…Obesity and obesity-related complications are linked to visceral adipose tissue. Despite this, it is unclear how visceral adipose tissue interacts with obesity-related metabolic complications [ 107 ].…”

“…A number of novel analyses have been introduced to identify functional enrichment pathways, protein–protein interactions, and network analyses that aim to identify pathways that target transcription factors, microRNA, and regulatory networks [ 107 ]. An overview of these studies is provided below.…”

“…Using public datasets, one hundred and eighty-four differentially expressed genes in the visceral adipose tissue were identified in children with obesity based on the selected datasets [ 107 ]. From these 19 candidate hub genes, 19 target transcription factors and miRNAs were analyzed.…”

“…From these 19 candidate hub genes, 19 target transcription factors and miRNAs were analyzed. Several miRNAs identified in this study are linked to obesity-related pathways and diseases [ 107 ].…”