DNA methylation of genes regulating appetite and prediction of weight loss after bariatric surgery in obese individuals
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Epigenetic traits are influenced by clinical variables; interaction between DNA methylation (DNAmeth) and bariatric surgery-induced weight loss has been scarcely explored. We investigated whether DNAmeth of genes encoding for molecules/hormones regulating appetite, food intake or obesity could predict successful weight outcome following Roux-en-Y gastric bypass (RYGB).
Forty-five obese individuals with no known comorbidities were stratified accordingly to weight decrease one-year after RYGB (excess weight loss, EWL ≥ 50%: good responders, GR; EWL < 50%: worse responders, WR). DNAmeth of leptin (LEP), ghrelin (GHRL), ghrelin receptor (GHSR) and insulin-growth factor-2 (IGF2) was assessed before intervention. Single nucleotide polymorphisms of genes affecting DNAmeth, DNMT3A and DNMT3B, were also determined.
At baseline, type 2 diabetes was diagnosed by OGTT in 13 patients. Post-operatively, GR (n = 23) and WR (n = 22) achieved an EWL of 67.7 ± 9.6 vs 38.2 ± 9.0%, respectively. Baseline DNAmeth did not differ between GR and WR for any tested genes, even when the analysis was restricted to subjects with no diabetes. A relationship between GHRL and LEP methylation profiles emerged (r = 0.47, p = 0.001). Searching for correlation between DNAmeth of the studied genes with demographic characteristics and baseline biochemical parameters of the studied population, we observed a correlation between IGF2 methylation and folate (r = 0.44, p = 0.003). Rs11683424 for DNMT3A and rs2424913 for DNMT3B did not correlate with DNAmeth of the studied genes.
In severely obese subjects, the degree of DNAmeth of some genes affecting obesity and related conditions does not work as predictor of successful response to RYGB.
KeywordsEpigenetics DNA methylation Appetite Bariatric surgery
This study has been supported by two grants from the University of Pisa.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest regarding the publication of this paper.
All procedures performed in human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Research involving human participants and/or animals
The ethics committee of the University of Pisa approved the protocol.
Informed consent was obtained from all individual participants included in the study.
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