Transcriptomic analysis of palmitoylation-related genes reveals a preferential association with BCAA catabolism in adipose tissue from pediatric obesity.

BACKGROUND: Pediatric obesity is a major public health challenge with adverse effects on health and long-term metabolic outcomes. Although diet and genetic susceptibility contribute to obesity across the life course, pediatric obesity may be particularly influenced by early-life developmental and maternal factors. Protein palmitoylation is linked to lipid metabolism, but whether palmitoylation-related programs differ between pediatric and adult obesity remains unclear. METHODS: We analyzed transcriptomic datasets from pediatric and adult obesity using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Candidate genes were further evaluated in a juvenile high-fat diet-induced obesity mouse model and online obesity databases. RESULTS: In both age groups, palmitoylation-related candidate common hub genes were significantly enriched in lipid metabolic pathways. However, pediatric-specific palmitoylation-related candidate common hub genes were prominently enriched in branched-chain amino acid (BCAA) metabolic and catabolic processes. Least absolute shrinkage and selection operator regression prioritized seven candidate genes. In the juvenile obesity model, four genes (Cldn2, Mccc2, Pcca, and Vdac2) were consistently downregulated in adipose tissue from obese offspring, correlating significantly with fat mass. Downregulation was less pronounced in obese adult mice, whereas total protein palmitoylation was markedly elevated in both age groups, with a greater increase in juveniles. Of the four genes, Mccc2 and Pcca were directly involved in BCAA catabolism, suggesting an association between BCAA metabolism and pediatric obesity. CONCLUSION: These findings provide a basis for future mechanistic studies of age-related differences in adipose tissue metabolism in obesity.