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

M Ahrens, O Ammerpohl, W von Schönfels, J Kolarova… - Cell metabolism, 2013 - cell.com
M Ahrens, O Ammerpohl, W von Schönfels, J Kolarova, S Bens, T Itzel, A Teufel, A Herrmann…
Cell metabolism, 2013cell.com
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 …
Summary
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.
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