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

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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Ahrens M,Ammerpohl O,von Schönfels W,Kolarova J,Bens S,Itzel T,Teufel A,Herrmann A,Brosch M,Hinrichsen H,Erhart W,Egberts J,Sipos B,Schreiber S,Häsler R,Stickel F,Becker T,Krawczak M,Röcken C,Siebert R,Schafmayer

doi

10.1016/j.cmet.2013.07.004

subject

Has Abstract

pub_date

2013-08-06 00:00:00

pages

296-302

issue

2

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(13)00293-3

journal_volume

18

pub_type

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