Journal
INTERNATIONAL JOURNAL OF OBESITY
Volume 42, Issue 3, Pages 412-423Publisher
SPRINGERNATURE
DOI: 10.1038/ijo.2017.245
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Funding
- Academy of Finland [307339, 251316, 259926, 297908, 266286, 265240, 263278]
- Sigrid Juselius Foundation
- University of Helsinki Research Funds
- Helsinki University Hospital Research Funds
- Paulo Foundation
- Finnish Cultural Foundation Southwest Finland Regional Fund
- Turku University Hospital Research Funds
- Academy of Finland Centre of Excellence in Research on Mitochondria, Metabolism and Disease [272376]
- Novo Nordisk Foundation
- Biomedicum Helsinki Foundation
- Finnish Diabetes Research Foundation
- Jalmari and Rauha Ahokas Foundation
- Finnish Foundation for Cardiovascular Research
- EPITRAIN-FP7-PEOPLE-ITN [316758]
- Doctoral Programme in Population Health, University of Helsinki
- Novo Nordisk Fonden [NNF10OC1013354, NNF17OC0027232] Funding Source: researchfish
- Academy of Finland (AKA) [307339, 307339] Funding Source: Academy of Finland (AKA)
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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. PARTICIPANTS/METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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