A1 Refereed original research article in a scientific journal
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss
Authors: S Bollepalli, S Kaye, S Heinonen, J Kaprio, A Rissanen, KA Virtanen, K Pietiläinen, M Ollikainen
Publisher: Nature Publishing Group
Publication year: 2018
Journal: International Journal of Obesity
Journal name in source: International Journal of Obesity
Volume: 42
Issue: 3
First page : 412
Last page: 423
Number of pages: 12
ISSN: 0307-0565
DOI: https://doi.org/10.1038/ijo.2017.245
Background:
Few
studies have examined both gene expression and DNA methylation profiles
in subcutaneous adipose tissue (SAT) during long-term weight loss.
Thus, molecular mechanisms in weight loss and regain remain elusive.
We performed a 1-year weight loss intervention on 19 healthy obese participants (mean body mass index (BMI) 34.6 kg m−2)
and studied longitudinal gene expression (Affymetrix Human Genome U133
Plus 2.0) and DNA methylation (Infinium HumanMethylation450 BeadChip) in
SAT at 0, 5 and 12 months. To examine whether weight loss and acquired
obesity produce reciprocal profiles, we verified our findings in 26
BMI-discordant monozygotic twin pairs.
We
found altered expression of 69 genes from 0 to 5’ months (short-term)
weight loss. Sixty of these genes showed reversed expression in acquired
obesity (twins). Altogether 21/69 genes showed significant
expression–DNA methylation correlations. Pathway analyses revealed
increased high-density lipoprotein-mediated lipid transport
characteristic to short-term weight loss. After the fifth month, two
groups of participants evolved: weight losers (WLs) and weight regainers
(WRs). In WLs five genes were differentially expressed in 5 vs 12
months, three of which significantly correlated with methylation.
Signaling by insulin receptor pathway showed increased expression. We
further identified 35 genes with differential expression in WLs from 0
to 12 months (long-term) weight loss, with 20 showing opposite
expression patterns in acquired obesity, and 16/35 genes with
significant expression–DNA methylation correlations. Pathway analyses
demonstrated changes in signal transduction, metabolism, immune system
and cell cycle. Notably, seven genes (UCHL1, BAG3, TNMD, LEP, BHMT2, EPDR1 and OSTM1) were found to be downregulated during both short- and long-term weight loss.
Our
study indicates short- and long-term weight loss influences in
transcription and DNA methylation in SAT of healthy participants.
Moreover, we demonstrate that same genes react in an opposite manner in
weight loss and acquired obesity.
