BACKGROUND Severe obesity is a growing, worldwide burden and conventional therapies including radical change of diet and/or increased physical activity have limited results. Bariatric surgery has been proposed as an alternative therapy showing promising results. It leads to substantial weight loss and improvement of comorbidities such as type 2 diabetes. Increased adiposity is associated with changes in epigenetic profile, including DNA methylation. We investigated the effect of bariatric surgery on clinical profile, DNA methylation, and biological age estimated using Horvath's epigenetic clock. RESULTS To determine the impact of bariatric surgery and subsequent weight loss on clinical traits, a cohort of 40 severely obese individuals (BMI = 30-73 kg/m2) was examined at the time of surgery and at three follow-up visits, i.e., 3, 6, and 12 months after surgery. The majority of the individuals were women (65%) and the mean age at surgery was 45.1 ± 8.1 years. We observed a significant decrease over time in BMI, fasting glucose, HbA1c, HOMA-IR, insulin, total cholesterol, triglycerides, LDL and free fatty acids levels, and a significant small increase in HDL levels (all p values < 0.05). Epigenome-wide association analysis revealed 4857 differentially methylated CpG sites 12 months after surgery (at Bonferroni-corrected p value < 1.09 × 10-7). Including BMI change in the model decreased the number of significantly differentially methylated CpG sites by 51%. Gene set enrichment analysis identified overrepresentation of multiple processes including regulation of transcription, RNA metabolic, and biosynthetic processes in the cell. Bariatric surgery in severely obese patients resulted in a decrease in both biological age and epigenetic age acceleration (EAA) (mean = - 0.92, p value = 0.039). CONCLUSIONS Our study shows that bariatric surgery leads to substantial BMI decrease and improvement of clinical outcomes observed 12 months after surgery. These changes explained part of the association between bariatric surgery and DNA methylation. We also observed a small, but significant improvement of biological age. These epigenetic changes may be modifiable by environmental lifestyle factors and could be used as potential biomarkers for obesity and in the future for obesity related comorbidities.

中文翻译：

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减肥手术对严重肥胖患者临床特征、DNA 甲基化和衰老的影响。

背景严重肥胖症是一个不断增长的世界范围的负担，而包括彻底改变饮食和/或增加身体活动在内的常规疗法的效果有限。减肥手术已被提议作为一种替代疗法，显示出有希望的结果。它可以显着减轻体重并改善 2 型糖尿病等并发症。肥胖增加与表观遗传谱的变化有关，包括 DNA 甲基化。我们研究了减肥手术对使用 Horvath 表观遗传时钟估计的临床特征、DNA 甲基化和生物学年龄的影响。结果 为了确定减肥手术和随后的体重减轻对临床特征的影响，在手术时和三次随访时检查了 40 名严重肥胖个体（BMI = 30-73 kg/m2）的队列，即， 3, 6, 和手术后 12 个月。大多数个体是女性 (65%)，平均手术年龄为 45.1 ± 8.1 岁。我们观察到 BMI、空腹血糖、HbA1c、HOMA-IR、胰岛素、总胆固醇、甘油三酯、低密度脂蛋白和游离脂肪酸水平随时间显着降低，而高密度脂蛋白水平显着小幅增加（所有 p 值 < 0.05）。表观基因组关联分析显示手术后 12 个月有 4857 个差异甲基化的 CpG 位点（Bonferroni 校正的 p 值 < 1.09 × 10-7）。在模型中包括 BMI 变化后，显着差异甲基化的 CpG 位点的数量减少了 51%。基因集富集分析确定了多个过程的过度表达，包括细胞中转录、RNA 代谢和生物合成过程的调节。严重肥胖患者的减肥手术导致生物学年龄和表观遗传年龄加速 (EAA) 降低（平均值 = - 0.92，p 值 = 0.039）。结论 我们的研究表明，在手术后 12 个月观察到，减肥手术可显着降低 BMI 并改善临床结果。这些变化部分解释了减肥手术与 DNA 甲基化之间的关联。我们还观察到生物年龄的微小但显着的改善。这些表观遗传变化可能会受到环境生活方式因素的影响，并可用作肥胖和未来肥胖相关合并症的潜在生物标志物。结论 我们的研究表明，在手术后 12 个月观察到，减肥手术可显着降低 BMI 并改善临床结果。这些变化部分解释了减肥手术与 DNA 甲基化之间的关联。我们还观察到生物年龄的微小但显着的改善。这些表观遗传变化可能会受到环境生活方式因素的影响，并可用作肥胖和未来肥胖相关合并症的潜在生物标志物。结论 我们的研究表明，在手术后 12 个月观察到，减肥手术可显着降低 BMI 并改善临床结果。这些变化部分解释了减肥手术与 DNA 甲基化之间的关联。我们还观察到生物年龄的微小但显着的改善。这些表观遗传变化可能会受到环境生活方式因素的影响，并可用作肥胖和未来肥胖相关合并症的潜在生物标志物。