Investigation of changes in DNA methylation associated with alterations in gene expression resulting in differences between lean and obese adipogenesis

Elsevier

Available online 14 April 2023, 110623

GenomicsAuthor links open overlay panel, , Highlights•

Alterations in DNA methylation that negatively or positively affect gene expression are associated with adipogenesis and obesity.

Lean adipogenesis depends on greater changes in DNA methylation than are needed for obese adipogenesis.

Promoter hypomethylation of PPARG, ADIPOQ and FABP4 is associated with higher expression levels of these genes in obese adipocytes than in lean adipocytes.

Various alterations in DNA methylation in the promoter and/or gene body contribute to the greater upregulation of inflammatory genes, including IL-6, IL-1β, and TNF-α, in lean adipocytes than in obese adipocytes.

Abstract

DNA methylation (DNAm) is an important epigenetic regulator controlling various cellular activities, including cell proliferation and differentiation. In the present work, we examined alterations in DNAm associated with obesity using methylome and transcriptome data from 27 purified adipocytes (ACs) and 7 preadipocytes (preACs) in human visceral adipose tissue (VAT) samples. We identified differentially methylated probes (DMPs) using two methods: (i) DMPs that were obtained from a comparison of the DNAm levels between AC and preAC samples (AGDMPs) and (ii) DMPs that were obtained from a comparison of the DNAm levels between obese and lean AC samples (ACDMPs). These two classes of DMPs were obtained to identify a relationship between adipogenesis and obesity. We also investigated how hyper and hypomethylation of the promoter and/or gene body differentially affected changes in gene expression by estimating the odds ratios (ORs) of changes in gene expression without DMPs in the background. Interestingly, the magnitude of DNAm alterations during AC differentiation was greater under lean conditions than under obese conditions. In conclusion, several adipogenesis-related genes were affected by complicated methylation changes and ultimately cause differences in gene expression in ACs under lean and obese conditions.

Keywords

Adipogenesis

Visceral adipose tissue

Obesity

DNA methylation

Gene expression

AbbreviationsKNIH

Korea National Institute of Health

SAT

subcutaneous adipose tissue

VAT

visceral adipose tissue

450 K

HumanMethylation450 BeadChip

DMP

differentially methylated probe

AGDMP

DMP by comparing ACs versus preACs

ACDMP

DMP by comparing L-ACs versus O-ACs

DEG

differentially expressed gene

AGDMP-DEG

DEG of AGDMP-harboring gene

DEM

differentially expressed miRNA

PCA

principal component analysis

DNMT

DNA methyltransferase

Data availability

The data are available in both the IHEC database (https://epigenomesportal.ca/ihec/index.html) and CODA database (https://codo.nih.go.kr/index.do, CODA accession number: R00315).

© 2023 The Authors. Published by Elsevier Inc.

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