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

Cell & Bioscience

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

[1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, 1954 Huashan Road, 200030, Shanghai, China;Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China;Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China;Shanghai Innovation Center of Traditional Chinese Medicine Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China;

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

DOI  :  10.1186/s13578-021-00701-6

来源: Springer

【 摘 要 】

BackgroundNonalcoholic 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.MethodsMethylation 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.ResultsBoth 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.ConclusionsWe 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 (ISRCTN 42622771)

【 授权许可】

CC BY