Laboratory of Nutrigenomics Studies, Department of Internal Medicine, Ribeirão Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.
Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.
BMC Med Genomics. 2019 May 27;12(1):72. doi: 10.1186/s12920-019-0522-7.
BACKGROUND/OBJECTIVES: Obesity has been associated with gene methylation regulation. Recent studies have shown that epigenetic signature plays a role in metabolic homeostasis after Roux-en Y gastric bypass (RYGB). To conduct a genome-wide epigenetic analysis in peripheral blood to investigate whether epigenetic changes following RYGB stem from weight loss or the surgical procedure per se.
SUBJECTS/METHODS: By means of the Infinium Human Methylation 450 BeadChip array, global methylation was analyzed in blood of 24 severely obese women before and 6 months after RYGB and in 24 normal-weight women (controls).
In blood cells, nine DMCpG sites showed low methylation levels before surgery, methylation levels increased after RYGB and neared the levels measured in the controls. Additionally, 44 CpG sites associated with the Wnt and p53 signaling pathways were always differently methylated in the severely obese patients as compared to the controls and were not influenced by RYGB. Finally, 1638 CpG sites related to inflammation, angiogenesis, and apoptosis presented distinct methylation in the post-surgery patients as compared to the controls.
Bariatric surgery per se acts on CpGs related to inflammation, angiogenesis, and endothelin-signaling. However, the gene cluster associated with obesity remains unchanged, suggesting that weight loss 6 months after RYGB surgery cannot promote this effect.
背景/目的：肥胖与基因甲基化调控有关。最近的研究表明，表观遗传特征在 Roux-en Y 胃旁路（RYGB）术后代谢稳态中发挥作用。本研究旨在通过对周围血进行全基因组表观遗传分析，探讨 RYGB 后发生的表观遗传变化是源于体重减轻还是手术本身。
受试者/方法：通过 Infinium Human Methylation 450 BeadChip 芯片，分析 24 例严重肥胖女性 RYGB 术前和术后 6 个月及 24 例正常体重女性（对照组）的外周血全基因组甲基化水平。
在血细胞中，有 9 个 DMCpG 位点在术前呈现低甲基化水平，RYGB 后甲基化水平增加，接近对照组的水平。此外，与 Wnt 和 p53 信号通路相关的 44 个 CpG 位点在严重肥胖患者中始终与对照组存在差异甲基化，不受 RYGB 的影响。最后，与炎症、血管生成和细胞凋亡相关的 1638 个 CpG 位点在术后患者中与对照组存在明显的甲基化差异。
RYGB 手术本身作用于与炎症、血管生成和内皮素信号相关的 CpG。然而，与肥胖相关的基因簇没有改变，这表明 RYGB 术后 6 个月的体重减轻不能促进这种效应。
