Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation

Cell & Bioscience

Guang He¹  Lei Ji¹  Xi Wu¹  Fan Yuan¹  Yan Bi¹  Xingwang Li¹  Kai Su¹  Zhenming Guo¹  Fengping Yang¹  Ke Han¹  Qing Lu¹  Xiao Yang¹  Yi Shi¹  Mofan Feng¹  Na Wu¹  Decheng Ren¹  Liangjie Liu¹  Shenglong Le²  Baocheng Liu³  Siran Yue³  Ruirui Wang³  Fengyan Jiang³ 

[1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University;Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University;Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine;

关键词: NAFLD;    NASH;    Exercise intervention;    Diet intervention;    DNA methylation;    GAB2;   

DOI  :  10.1186/s13578-021-00701-6

来源: DOAJ

【 摘 要 】

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 < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of 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. Trial registration International Standard Randomized Controlled Trial Number Register (ISRCTN 42622771)

【 授权许可】

Unknown