DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery

被引:435
作者
Ahrens, Markus [1 ,2 ]
Ammerpohl, Ole [2 ]
von Schoenfels, Witigo [1 ]
Kolarova, Julia [2 ]
Bens, Susanne [2 ]
Itzel, Timo [7 ]
Teufel, Andreas [7 ]
Herrmann, Alexander [3 ]
Brosch, Mario [3 ]
Hinrichsen, Holger [8 ]
Erhart, Wiebke [3 ]
Egberts, Jan [1 ]
Sipos, Bence [9 ]
Schreiber, Stefan [3 ]
Haesler, Robert [6 ]
Stickel, Felix [10 ]
Becker, Thomas [1 ]
Krawczak, Michael [4 ]
Roecken, Christoph [5 ]
Siebert, Reiner [2 ]
Schafmayer, Clemens [1 ]
Hampe, Jochen [3 ,11 ]
机构
[1] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gen & Thorac Surg, D-24015 Kiel, Germany
[2] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, D-24015 Kiel, Germany
[3] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Internal Med 1, D-24015 Kiel, Germany
[4] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Stat & Informat, D-24015 Kiel, Germany
[5] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Pathol, D-24015 Kiel, Germany
[6] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, D-24015 Kiel, Germany
[7] Univ Hosp Regensburg, Dept Internal Med 1, D-93053 Regensburg, Germany
[8] Gastroenterol & Hepatol Ctr Kiel, D-24105 Kiel, Germany
[9] Univ Tubingen Hosp, Inst Pathol, D-72074 Tubingen, Germany
[10] Univ Bern, Dept Clin Res Hepatol, CH-3010 Bern, Switzerland
[11] Univ Hosp Dresden, Dept Med 1, D-01307 Dresden, Germany
关键词
ATP-CITRATE LYASE; INSULIN-RESISTANCE; SKELETAL-MUSCLE; GROWTH; ASSOCIATION; METABOLISM; STEATOSIS; PROMOTER; GENOME; GENE;
D O I
10.1016/j.cmet.2013.07.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, IGFBP2, and PRKCE) and replicated by bisulfite pyrosequening (independent n = 39). Transcription factor binding sites at NAFLD-specific CpG sites were >1,000-fold enriched for ZNF274, PGC1A, and SREBP2. Intraindividual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Postbariatric and NAFLD-specific methylation signatures were clearly distinct both in gene ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1, and ESRRA sites. Our findings provide an example of treatment-induced epigenetic organ remodeling in humans.
引用
收藏
页码:296 / 302
页数:7
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