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Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A
Clarissa Berardo1,2, Valeria Calcaterra3,4, Alessia Mauri1,2
1Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science, University of Milan, 20157 Milan, Italy.
Insights
Severe obesity in children shows significant gene expression changes in subcutaneous fat. This study reveals key molecular differences in pediatric severe obesity compared to normal weight and milder forms.
Area of Science:
- Genomics
- Molecular Biology
- Pediatric Endocrinology
Background:
- Pediatric obesity is a growing global health concern.
- Understanding the molecular underpinnings of pediatric obesity is crucial for developing effective interventions.
- Omic approaches offer valuable insights into the pathophysiology of obesity.
Purpose of the Study:
- To identify transcriptional differences in subcutaneous adipose tissue (scAT) of children across a spectrum of weight status: normal weight (NW), overweight (OW), obesity (OB), and severe obesity (SV).
- To investigate the molecular pathways associated with severe pediatric obesity.
Main Methods:
- Collected periumbilical scAT biopsies from 20 male children (aged 1-12 years) stratified into NW, OW, OB, and SV groups based on BMI z-scores.
- Performed scAT RNA-Seq analysis and differential gene expression analysis using DESeq2.
- Conducted KEGG and Gene Set Enrichment Analysis (GSEA) to explore biological pathways.
Main Results:
- Significant deregulation of both coding and non-coding transcripts was observed in the severe obesity group compared to other weight categories.
- KEGG pathway analysis indicated that differentially expressed coding transcripts were primarily involved in lipid metabolism.
- GSEA revealed upregulation of lipid degradation, metabolism, bioenergetic processes, and branched-chain amino acid catabolism in severe obesity.
Conclusions:
- This study provides the first evidence of significant transcriptional deregulation in the scAT of children with severe obesity.
- The findings highlight distinct molecular signatures in severe pediatric obesity, particularly involving lipid and energy metabolism.
- These molecular insights could inform future therapeutic strategies for pediatric obesity.
Abstract:
The prevalence of pediatric obesity is rising rapidly worldwide, and "omic" approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1-12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity.
