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

Cell Metab. 2013 Aug 6;18(2):296-302. doi: 10.1016/j.cmet.2013.07.004.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bariatric Surgery / adverse effects*
  • DNA Methylation / genetics*
  • Fatty Liver / genetics*
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin / metabolism
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Obesity, Morbid / genetics
  • Obesity, Morbid / metabolism
  • Obesity, Morbid / surgery*
  • Signal Transduction / genetics


  • Insulin