Dataset Information

Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.

ABSTRACT:

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 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 years, BMI = 21.9 ± 3.0 kg/m²) or Obese (Ob; n = 15, age = 16 ± 2 years, 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 analyses.

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; 11/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. Upregulations in the PI3K/AKT signaling pathway mRNAs 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 pathways including PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by changes in DNA methylation.

SUBMITTER: Barberio MD

PROVIDER: S-EPMC6881970 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.

Barberio Matthew D MD Nadler Evan P EP Sevilla Samantha S Lu Rosemary R Harmon Brennan B Hubal Monica J MJ

Diabetology & metabolic syndrome 20191127

<h4>Background</h4>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 are altered in VAT from obese compared to non-obese youth.<h4>Methods</h4>VAT samples from adolescent females grouped as Lean (L; n = 15; age = 15 ± 3 years, BMI = 21.9 ± 3.0 kg/ ...[more]

PMID: 31798691

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Project description:Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, γδ T, and Treg cell populations in VAT and blood of healthy lean subjects revealed that CD56hi NK and OX40+ Treg cells are more abundant in VAT with respect to blood. Conversely, CD56dim NK and total Treg cells are most present in the circulation, while γδ T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated Treg cells, and a concomitant preferential enrichment of OX40-expressing Treg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the Vγ9Vδ2/γδ T cell ratio at systemic level. The alterations in the relative proportions of Treg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes.

Dataset Information

Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.

Background

Methods

Results

Conclusion

Publications

Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.

Similar Datasets

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