DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.

Authors:
Markus Ahrens, Ole Ammerpohl, Witigo von Schönfels, Julia Kolarova, Susanne Bens, Timo Itzel, Andreas Teufel, Alexander Herrmann, Mario Brosch, Holger Hinrichsen, Wiebke Erhart, Jan Egberts, Bence Sipos, Stefan Schreiber, Robert Häsler, Felix Stickel, Thomas Becker, Michael Krawczak, Christoph Röcken, Reiner Siebert, Clemens Schafmayer, Jochen Hampe
Year of publication:
2013
Volume:
18
Issue:
2
Issn:
1550-4131
Journal title abbreviated:
CELL METAB
Journal title long:
Cell metabolism
Impact factor:
17.303
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.