Available online 14 April 2023, 110623
Author 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.
AbstractDNA 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.
KeywordsAdipogenesis
Visceral adipose tissue
Obesity
DNA methylation
Gene expression
AbbreviationsKNIHKorea National Institute of Health
SATsubcutaneous adipose tissue
VATvisceral adipose tissue
450 KHumanMethylation450 BeadChip
DMPdifferentially methylated probe
AGDMPDMP by comparing ACs versus preACs
ACDMPDMP by comparing L-ACs versus O-ACs
DEGdifferentially expressed gene
AGDMP-DEGDEG of AGDMP-harboring gene
DEMdifferentially expressed miRNA
PCAprincipal component analysis
DNMTDNA methyltransferase
Data availabilityThe 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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