Human Nutrition Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, England.
Surgery Department, Northumbria NHS Foundation Trust, Newcastle upon Tyne, England.
Int J Obes (Lond). 2023 Dec;47(12):1278-1285. doi: 10.1038/s41366-023-01384-4. Epub 2023 Sep 15.
DNA methylation is an epigenetic mechanism through which environmental factors including nutrition and inflammation influence health. Obesity is a major modifiable risk factor for many common diseases including cardiovascular diseases and cancer. In particular, obesity-induced inflammation resulting from aberrantly-methylated inflammatory genes may drive risk of several non-communicable diseases including colorectal cancer (CRC). This study is the first to investigate the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in the rectum and in cell-free DNA (cfDNA) from blood.
DNA methylation was quantified in rectal mucosal biopsies and cfDNA from serum of 28 participants with obesity before and 6 months after BS, as well as in 12 participants without obesity (control group) matched for age and sex from the Biomarkers Of Colorectal cancer After Bariatric Surgery (BOCABS) Study. DNA methylation of LEP, IL6, POMC, LINE1, MAPK7 and COX2 was quantified by pyrosequencing.
BMI decreased significantly from 41.8 kg/m pre-surgery to 32.3 kg/m at 6 months after BS. Compared with the control group, obesity was associated with lower LEP methylation in both the rectal mucosa and in cfDNA from serum. BS normalised LEP methylation in DNA from the rectal mucosa but not in cfDNA. BS decreased methylation of some CpG sites of LINE1 in the rectal mucosal DNA and in cfDNA to levels comparable with those in participants without obesity. Methylation of POMC in rectal mucosal DNA was normalised at 6 months after BS.
BS reversed LINE1, POMC and LEP methylation in the rectal mucosa of patients with obesity to levels similar to those in individuals without obesity. These findings support current evidence of effects of BS-induced weight loss on reversibility of DNA methylation in other tissues. The DNA methylation changes in the rectal mucosa shows promise as a biomarker for objective assessment of effects of weight loss interventions on risk of cancer and other diseases.
DNA 甲基化是一种表观遗传机制，通过该机制，包括营养和炎症在内的环境因素会影响健康。肥胖是许多常见疾病（包括心血管疾病和癌症）的主要可改变风险因素。具体而言，肥胖引起的炎症会导致异常甲基化的炎症基因，从而可能导致包括结直肠癌（CRC）在内的几种非传染性疾病的风险增加。这项研究首次调查了减肥手术（BS）引起的体重减轻对直肠和血液中无细胞 DNA（cfDNA）中 DNA 甲基化的影响。
对 28 名肥胖参与者进行了 BS 前后直肠黏膜活检和血清 cfDNA 的 DNA 甲基化定量，以及对 12 名肥胖对照组（来自 Biomarkers Of Colorectal cancer After Bariatric Surgery 研究）的参与者进行了年龄和性别匹配的直肠黏膜活检和血清 cfDNA 的 DNA 甲基化定量。通过焦磷酸测序定量 LEP、IL6、POMC、LINE1、MAPK7 和 COX2 的 DNA 甲基化。
BMI 从术前的 41.8kg/m2 显著下降到 BS 后 6 个月的 32.3kg/m2。与对照组相比，肥胖与直肠黏膜和血清 cfDNA 中的 LEP 甲基化水平降低有关。BS 使直肠黏膜中的 LEP 甲基化正常化，但 cfDNA 中未发生变化。BS 降低了直肠黏膜 DNA 和 cfDNA 中一些 LINE1 的 CpG 位点的甲基化，使其达到与非肥胖参与者相似的水平。BS 后 6 个月 POMC 在直肠黏膜 DNA 中的甲基化正常化。
BS 使肥胖患者直肠黏膜中的 LINE1、POMC 和 LEP 甲基化恢复到与非肥胖个体相似的水平。这些发现支持减肥手术引起的体重减轻对其他组织中 DNA 甲基化逆转的现有证据。直肠黏膜中的 DNA 甲基化变化有望成为评估减肥干预对癌症和其他疾病风险影响的客观生物标志物。
