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

Ahrens, Markus and Ammerpohl, Ole and von Schoenfels, Witigo and Kolarova, Julia and Bens, Susanne and Itzel, Timo and Teufel, Andreas and Herrmann, Alexander and Brosch, Mario and Hinrichsen, Holger and Erhart, Wiebke and Egberts, Jan and Sipos, Bence and Schreiber, Stefan and Haesler, Robert and Stickel, Felix and Becker, Thomas and Krawczak, Michael and Roecken, Christoph and Siebert, Reiner and Schafmayer, Clemens and Hampe, Jochen (2013) DNA Methylation Analysis in Nonalcoholic Fatty Liver Disease Suggests Distinct Disease-Specific and Remodeling Signatures after Bariatric Surgery. CELL METABOLISM, 18 (2). pp. 296-302. ISSN 1550-4131, 1932-7420

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: ATP-CITRATE LYASE; INSULIN-RESISTANCE; SKELETAL-MUSCLE; GROWTH; ASSOCIATION; METABOLISM; STEATOSIS; PROMOTER; GENOME; GENE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Apr 2020 11:52
Last Modified: 02 Apr 2020 11:52
URI: https://pred.uni-regensburg.de/id/eprint/16237

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