血液甲基化模式反映了减肥手术后脂肪组织的表观遗传重塑。

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL EBioMedicine Pub Date : 2024-08-01 Epub Date: 2024-07-13 DOI:10.1016/j.ebiom.2024.105242
Luise Müller, Anne Hoffmann, Stephan H Bernhart, Adhideb Ghosh, Jiawei Zhong, Tobias Hagemann, Wenfei Sun, Hua Dong, Falko Noé, Christian Wolfrum, Arne Dietrich, Michael Stumvoll, Lucas Massier, Matthias Blüher, Peter Kovacs, Rima Chakaroun, Maria Keller
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引用次数: 0

摘要

背景:有关减肥手术后DNA甲基化的研究主要集中在血细胞上,而对于减肥手术在多大程度上反映了特定代谢相关器官(如脂肪组织)的DNA甲基化情况尚不清楚。在此,我们研究了减肥手术后脂肪组织库的特定甲基化变化是否反映在血液中:方法:利用 Illumina 850K EPIC 技术,我们分析了九名重度肥胖患者(N = 6 名女性)手术前后配对血液、皮下和网膜内脏 AT(SAT/OVAT)样本的全基因组 DNA 甲基化情况:与血液(9267个DMRs,从-8.8%到7.7%)相比,减肥手术后内脏AT(SAT:12865个DMRs,从-11.5%到10.8%;OVAT:14632个DMRs,从-13.7%到12.8%)中差异甲基化区域(DMRs)的数量和效应大小更为明显。跨组织 DMRs 涉及免疫相关基因。其中,49个区域可与独立个体血液中相似的甲基化变化进行验证。14个DMRs与减肥术后AT中不同表达基因相关,包括PIK3AP1在SAT和OVAT中的下调。与血液相比,肥胖症患者的DNA甲基化年龄加速度明显更高,但手术后仍不受影响:解释:血液和腹腔镜手术中同时发生的甲基化模式变化,尤其是免疫相关基因的变化,表明血液中的DNA甲基化反映了腹腔镜手术后的炎症状态:经费来源见致谢部分。
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Blood methylation pattern reflects epigenetic remodelling in adipose tissue after bariatric surgery.

Background: Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue. Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood.

Methods: Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals (N = 6 female) with severe obesity pre- and post-surgery.

Findings: The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from -11.5 to 10.8%; OVAT: 14,632 DMRs from -13.7 to 12.8%) than in blood (9267 DMRs from -8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49 regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery.

Interpretation: Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors AT's inflammatory state post-bariatric surgery.

Funding: The funding sources are listed in the Acknowledgments section.

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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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