1. Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
- Author
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Fengyan Jiang, Xingwang Li, Fan Yuan, Kai Su, Guang He, Bao-Cheng Liu, Yan Bi, Xiao Yang, Zhenming Guo, Ruirui Wang, Shenglong Le, Liangjie Liu, Mofan Feng, Xi Wu, Decheng Ren, Fengping Yang, Qing Lu, Ke Han, Yi Shi, Lei Ji, Na Wu, and Siran Yue
- Subjects
medicine.medical_specialty ,QH301-705.5 ,Diet intervention ,Adipose tissue ,QD415-436 ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Internal medicine ,NAFLD ,Nonalcoholic fatty liver disease ,medicine ,Exercise intervention ,Epigenetics ,Biology (General) ,GAB2 ,DNA methylation ,business.industry ,Research ,NASH ,nutritional and metabolic diseases ,Promoter ,Methylation ,medicine.disease ,digestive system diseases ,Endocrinology ,CpG site ,Steatosis ,business ,TP248.13-248.65 ,Biotechnology - Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2. Methods Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used. Results Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention. Conclusions We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trialregistration International Standard Randomized Controlled Trial Number Register (ISRCTN42622771)
- Published
- 2021