Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass
Altered promoter methylation of PDK4, IL1 B, IL6, and TNF after Roux-en Y gastric bypass
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DOI：
10.1016/j.soard.2013.12.019
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Naslund, Erik
中科院分区：
文献类型：
--
作者：
Kirchner, Henriette;Nylen, Carolina;Naslund, Erik
背景资料：Roux-en Y胃旁路术（RYGB）的早期益处部分是由患者在手术前和手术后急性接受的热量限制介导的。改变的DNA甲基化发生在包括肥胖在内的代谢疾病中，以及RYGB后8个月的骨骼肌中。本研究的目的是检测过氧化物酶体增殖物激活受体γ辅激活因子1-α的启动子甲基化是否在极低热量饮食（VLCD）或RYGB后，血液中的PPARGC 1 A、丙酮酸脱氢酶激酶同工酶-4（PDK 4）、转录因子A（TFAM）、白细胞介素-1 β（IL 1 B）、白细胞介素-6（IL 6）和肿瘤坏死因子-α（TNF）发生改变。非糖尿病肥胖患者（n = 18，体重指数[BMI] 42.3 +/- 4.9 kg/m2）接受了14天的VLCD，随后进行RYGB。非肥胖患者（n = 6，BMI 25.7 +/- 2.1 kg/m2）行择期胆囊切除术作为对照。在VLCD前后测量全血中选定启动子区域的DNA甲基化。在RYGB后1-2天和12 +/- 3个月对7名患者的亚组进行了研究。采用甲基化DNA捕获和实时定量PCR检测PPARGC 1A基因启动子甲基化水平。RYGB后两天改变PPARGC 1A、TFAM、IL 1 B、IL 6和TNF启动子的甲基化。胆囊切除术后第一天也观察到类似的变化。RYGB处理后12个月，PDK 4、IL 1 B、IL 6和TNF基因启动子甲基化水平升高。结论：RYGB处理后全血中受试基因启动子的表观遗传学改变比VLCD处理后更明显。DNA甲基化的变化可能有助于RYGB后整体代谢健康的改善。(C)2014年美国代谢和减肥外科学会。All rights reserved.
Background: Early benefits of Roux-en Y gastric bypass (RYGB) are partly mediated by the caloric restriction that patients undergo before and acutely after the procedure. Altered DNA methylation occurs in metabolic diseases including obesity, as well as in skeletal, muscle eight months after RYGB. The objective of this study was to test whether promoter methylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1 A), pyruvate dehydrogenase kinase isozyme-4 (PDK4), transcription factor A (TFAM), interleulcin-1 beta (IL1 B), interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF) is altered in blood after a very low calorie diet (VLCD) or RYGB.Methods: Obese nondiabetic patients (n = 18, body mass index [BMI] 42.3 +/- 4.9 kg/m(2)) underwent a 14-day VLCD followed by RYGB. Nonobese patients (n = 6, BMI 25.7 +/- 2.1 kg/m(2)) undergoing elective cholecystectomy served as controls. DNA methylation of selected promoter regions was measured in whole blood before and after VLCD. A subgroup of seven patients was studied 1-2 days and 12 +/- 3 months after RYGB. Promoter methylation was measured using methylated DNA capture and quantitative real-time polymerase chain reaction (PCR).Results: VLCD decreased promoter methylation of PPARGC1 A. Methylation of PPARGC1 A, TFAM, IL1 B, IL6, and TNF promoters was changed two days after RYGB. Similar changes were also seen on day one after cholecystectomy. Moreover, methylation increased in PDK4, IL1 B, IL6, and TNF promoters 12 months after RYGB.Conclusion: RYGB induced more profound epigenetic changes than VLCD in promoters of the tested genes in whole blood. Changes in DNA methylation may contribute to the improved overall metabolic health after RYGB. (C) 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.