Status of hepatic DNA methylome predetermines and modulates the severity of non-alcoholic fatty liver injury in miceReportar como inadecuado

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BMC Genomics

, 17:298

Human and rodent genomics


BackgroundNonalcoholic 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.

ResultsIn 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.

ConclusionOur 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.

KeywordsDNA methylation Non-alcoholic fatty liver injury Susceptibility Mouse Inter-strain differences AbbreviationsCFDcholine- and folate-deficient

GWASgenome-wide association studies

MeDIPmethylated DNA immunoprecipitation

NAFLDnonalcoholic fatty liver disease

NASHnonalcoholic steatohepatitis

qRT-PCRquantitative reverse-transcription polymerase chain reaction

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-2617-2 contains supplementary material, which is available to authorized users.

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Autor: Volodymyr P. Tryndyak - Tao Han - James C. Fuscoe - Sharon A. Ross - Frederick A. Beland - Igor P. Pogribny


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