The evaluation for CpG island methylation of FASN and SREBP promoter in Mongolian gerbils NAFLD model

Abstract

IntroductionThe methylation of CpG island in promoter and its nearby area is one of the most important way to inhibit gene expression. The aim of this study was to examine the potential relationship between the CpG island methylation for fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP-1).Material and methodsTen newborn pups of gerbils as NB group, 10 adult gerbils with normal diet as control group, 10 adults with high-fat diet as NAFLD group, and 10 8-month-old as aged group. Blood and liver samples were collected for serum lipid detection and histopathology. A pyrosequencing technique was employed to determine the methylation rate. Then, the transcription and expression level for FASN and SREBP-1 were verified.ResultsSerum chelosterol and triglyceride was significantly increased in NAFLD and aged group (vs. control, P<0.05). The gerbils in NAFLD and aged group also showed obvious hepatic steatosis confirmed by histological examination. Control group had the highest methylation rate for FASN and SREBP-1, which were reduced in NAFLD and aged group. Except for NB group, both the transcription and expression levels of SREBP-1 and FASN genes were presented control group> Aged group > NAFLD group. Genes of SREBP and FASN showed a trend of hypomethylation in the NAFLD gerbil model.ConclusionsThe expression of SREBP gene tended to decrease, while the expression of FASN gene tended to increase with the age and disease development. FASN and SREBP-1 methylation might be a new method to evaluate NAFLD animal model and an available target for genetic marker screening.