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

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• 作者：Markus Ahrens ; Ole Ammerpohl ; Witigo von?Sch?nfels ; Julia Kolarova ; Susanne Bens ; Timo Itzel ; Andreas Teufel ; Alex ; er Herrmann ; Mario Brosch ; Holger Hinrichsen ; Wiebke Erhart ; Jan Egberts ; Bence Sipos ; Stefan Schreiber ; Robert H?sler ; Felix Stickel ; Thomas Becker ; Michael Krawczak ; Christoph R?cken ; Reiner Siebert ; et al.
• 刊名：Cell Metabolism
• 出版年：2013
• 出版时间：6 August, 2013
• 年：2013
• 卷：18
• 期：2
• 页码：296-302
• 全文大小：928 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences<h3 class=""h3"">Summaryh3>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.