Status of hepatic DNA methylome predetermines and modulates the severity of non-alcoholic fatty liver injury in mice.

Author(s): Tryndyak VP,  Han T,  Fuscoe JC,  Ross SA,  Beland FA,  Pogribny IP

Journal: BMC Genomics

Date: 2016 Apr 22

Major Program(s) or Research Group(s): NSRG

PubMed ID: 27103143

PMC ID: PMC4840954

Abstract: BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and Western countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD; nonetheless, the effect of inter-individual differences in the normal liver epigenome with regard to the susceptibility to NAFLD has not been determined. RESULTS: In the present study, we investigated the association between the DNA methylation status in the livers of A/J and WSB/EiJ mice and the severity of NAFLD-associated liver injury. We demonstrate that A/J and WSB/EiJ mice, which are characterized by significant differences in the severity of liver injury induced by a choline- and folate-deficient (CFD) diet exhibit substantial differences in cytosine DNA methylation in their normal livers. Furthermore, feeding A/J and WSB/EiJ mice a CFD diet for 12 weeks resulted in different trends and changes in hepatic cytosine DNA methylation. CONCLUSION: Our findings indicate a primary role of hepatic DNA methylation in the pathogenesis of NAFLD and suggest that individual variations in DNA methylation across the genome may be a factor determining and influencing the vulnerability to NAFLD.