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不同减肥手术方式对糖尿病和非糖尿病病态肥胖患者LINE-1 DNA甲基化无影响。

No effect of different bariatric surgery procedures on LINE-1 DNA methylation in diabetic and nondiabetic morbidly obese patients.

作者信息

Martín-Núñez G M, Cabrera-Mulero A, Alcaide-Torres J, García-Fuentes E, Tinahones F J, Morcillo S

机构信息

Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clínico Virgen de la Victoria, Málaga, Spain.

Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain; CIBER Pathophysiology of Obesity and Nutrition, Málaga, Spain.

出版信息

Surg Obes Relat Dis. 2017 Mar;13(3):442-450. doi: 10.1016/j.soard.2016.10.014. Epub 2016 Oct 21.

DOI:10.1016/j.soard.2016.10.014
PMID:27986580
Abstract

BACKGROUND

Bariatric surgery (BS) is proposed as a highly effective therapy for reducing weight and improving obesity-related co-morbidities. The molecular mechanisms involved in the metabolic improvement after BS are not completely resolved. Epigenetic modifications could have an important role.

OBJECTIVE

The aim of this study was to evaluate the effect of different BS procedures (Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy) on global DNA methylation (long interspersed nucleotide element 1 [LINE-1]) in a group of nondiabetic and diabetic severely obese patients.

SETTING

University hospital, Spain.

METHODS

This study included 60 patients (30 nondiabetic and 30 diabetic severely obese patients) undergoing BS: 31 patients underwent Roux-en-Y gastric bypass and 29 underwent laparoscopic sleeve gastrectomy. Before and 6 months post-BS, anthropometric data, blood pressure, and metabolic parameters were determined. LINE-1 DNA methylation was quantified by pyrosequencing. We used the methylation levels of tumor necrosis factor-α as a control gene promoter.

RESULTS

There were no differences between LINE-1 methylation levels at baseline and at 6 months after surgery (66.3±1.6 versus 66.2±2.06). Likewise, there was no statistically significant difference on LINE-1 methylation levels when we stratified according to metabolic status (diabetic versus nondiabetic), nor was there regarding the BS procedure. A strong correlation was shown between LINE-1 methylation levels and weight at baseline both in diabetic and nondiabetic obese patients (r = .486; P<.001). Tumor necrosis factor-α methylation levels increased significantly after BS in the group of diabetic obese patients.

CONCLUSION

After BS, global LINE-1 methylation is not modified in the short term. More studies are required to determine if LINE-1 is a stable epigenetic marker, or, on the contrary, if it is susceptible to modification by external factors such as changes in lifestyle or a surgical intervention.

摘要

背景

减重手术(BS)被认为是一种减轻体重和改善肥胖相关合并症的高效疗法。BS术后代谢改善所涉及的分子机制尚未完全明确。表观遗传修饰可能起重要作用。

目的

本研究旨在评估不同的BS手术(Roux-en-Y胃旁路术和腹腔镜袖状胃切除术)对一组非糖尿病和糖尿病重度肥胖患者整体DNA甲基化(长散在核元件1[LINE-1])的影响。

地点

西班牙大学医院。

方法

本研究纳入60例行BS的患者(30例非糖尿病和30例糖尿病重度肥胖患者):31例行Roux-en-Y胃旁路术,29例行腹腔镜袖状胃切除术。在BS术前及术后6个月,测定人体测量数据、血压和代谢参数。通过焦磷酸测序对LINE-1 DNA甲基化进行定量。我们将肿瘤坏死因子-α的甲基化水平用作对照基因启动子。

结果

基线时和术后6个月的LINE-1甲基化水平无差异(66.3±1.6对66.2±2.06)。同样,根据代谢状态(糖尿病与非糖尿病)分层时,LINE-1甲基化水平无统计学显著差异,不同的BS手术方式之间也无差异。在糖尿病和非糖尿病肥胖患者中,基线时LINE-1甲基化水平与体重之间均显示出强相关性(r = 0.486;P<0.001)。糖尿病肥胖患者组在BS术后肿瘤坏死因子-α甲基化水平显著升高。

结论

BS术后,短期内整体LINE-1甲基化未改变。需要更多研究来确定LINE-1是一个稳定的表观遗传标记,还是相反,它是否易受生活方式改变或手术干预等外部因素的影响。

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