PT  - JOURNAL ARTICLE
AU  - Matthew D. Barberio
AU  - Evan P. Nadler
AU  - Samantha Sevilla
AU  - Rosemary Lu
AU  - Brennan Harmon
AU  - Monica J. Hubal
TI  - Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity
AID  - 10.1101/728832
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 728832
4099  - http://biorxiv.org/content/early/2019/08/15/728832.short
4100  - http://biorxiv.org/content/early/2019/08/15/728832.full
AB  - Background Epigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways such as PI3K/AKT signaling are altered in VAT from obese compared to non-obese youth.Methods VAT samples from adolescent females grouped as Lean (L; n=15; age=15±3 yrs, BMI=21.9±3.0 kg/m2) or Obese (Ob; n=15, age=16±2 yrs, BMI=45.8±9.8 kg/m2) were collected. Global methylation (n=20) and gene expression (N=30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p<0.05), followed by biological pathway analysis.Results Overlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p=1.83×10−6; 10/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. mRNA upregulations in the PI3K/AKT Signaling Pathway genes TFAM (p=0.03; Fold change=1.8) and PPP2R5C (p=0.03, FC=2.6) were confirmed via qRT-PCR.Conclusion Our analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by obesity-related changes in DNA methylation.