Lovett Agnieszka, Hitman Graham A, Dimitriadis Georgios K, Murphy Alice M, Tripathi Gyanendra, Duggirala Aparna
OMICS Facility, Biomedical and Clinical Science Research Theme, School of Science, University of Derby, Derby DE22 1GB, UK.
Centre for Genomics and Child Health, Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, 4 Newark St., London E1 2AT, UK.
Epigenomes. 2025 Aug 29;9(3):32. doi: 10.3390/epigenomes9030032.
BACKGROUND/OBJECTIVES: Metabolic/bariatric surgery is currently the most successful treatment for patients with obesity; however, a fifth of patients undergoing surgery may not lose enough weight to be considered successful. Recent studies have shown that bariatric/metabolic surgery alters the epigenome and may explain postoperative improvements in metabolic health. The primary objective is to consolidate published differentially methylated CpG sites in pre- and post-metabolic/bariatric surgery female patients and associate them with the respective genes and pathways.
This systematic review adhered to the PRISMA-P guidelines and was registered with the PROSPERO (CRD42023421852). Following an initial screening of 541 studies using COVIDENCE, six studies were selected, comprising three epigenome-wide association studies (EWAS) and three candidate gene methylation studies. The published studies collected DNA samples from female patients with obesity before and after surgery (3 months, 6 months, 9-31 months, and 2 years). KEGG pathway analysis was performed on genes where the extracted CpG sites were located.
The meta-analysis showed that 11,456 CpG sites are differentially methylated after a successful weight loss surgery, with 109 sites mapped to genes involved in key metabolic pathways, including FoxO, mTOR, insulin, cAMP, adipocytokine, Toll-like receptor, and PI3K-Akt.
The highlighted differentially methylated CpG sites can be further used to predict the molecular signature associated with successful metabolic/bariatric surgery.
背景/目的：代谢/减重手术目前是肥胖患者最成功的治疗方法；然而，接受手术的患者中有五分之一可能体重减轻不足，不被视为手术成功。最近的研究表明，减重/代谢手术会改变表观基因组，这可能解释了术后代谢健康的改善。主要目的是汇总已发表的代谢/减重手术前后女性患者中差异甲基化的CpG位点，并将它们与各自的基因和通路相关联。
本系统评价遵循PRISMA-P指南，并在PROSPERO（CRD42023421852）注册。使用COVIDENCE对541项研究进行初步筛选后，选择了6项研究，包括3项全表观基因组关联研究（EWAS）和3项候选基因甲基化研究。已发表的研究收集了肥胖女性患者手术前后（3个月、6个月、9至31个月和2年）的DNA样本。对提取的CpG位点所在的基因进行KEGG通路分析。
荟萃分析表明，成功的减重手术后有11456个CpG位点发生差异甲基化，其中109个位点映射到参与关键代谢通路的基因，包括FoxO、mTOR、胰岛素、cAMP、脂肪细胞因子、Toll样受体和PI3K-Akt。
突出显示的差异甲基化CpG位点可进一步用于预测与成功的代谢/减重手术相关的分子特征。
