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

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 facto...

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Autores principales:	Na Wu, Fan Yuan, Siran Yue, Fengyan Jiang, Decheng Ren, Liangjie Liu, Yan Bi, Zhenming Guo, Lei Ji, Ke Han, Xiao Yang, Mofan Feng, Kai Su, Fengping Yang, Xi Wu, Qing Lu, Xingwang Li, Ruirui Wang, Baocheng Liu, Shenglong Le, Yi Shi, Guang He
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	NAFLD NASH Exercise intervention Diet intervention DNA methylation GAB2 Biotechnology TP248.13-248.65 Biology (General) QH301-705.5 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/ac3f2bdebfae42679d4160c6453e54c4
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spelling	oai:doaj.org-article:ac3f2bdebfae42679d4160c6453e54c42021-11-08T11:03:31ZEffect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation10.1186/s13578-021-00701-62045-3701https://doaj.org/article/ac3f2bdebfae42679d4160c6453e54c42021-11-01T00:00:00Zhttps://doi.org/10.1186/s13578-021-00701-6https://doaj.org/toc/2045-3701Abstract 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)Na WuFan YuanSiran YueFengyan JiangDecheng RenLiangjie LiuYan BiZhenming GuoLei JiKe HanXiao YangMofan FengKai SuFengping YangXi WuQing LuXingwang LiRuirui WangBaocheng LiuShenglong LeYi ShiGuang HeBMCarticleNAFLDNASHExercise interventionDiet interventionDNA methylationGAB2BiotechnologyTP248.13-248.65Biology (General)QH301-705.5BiochemistryQD415-436ENCell & Bioscience, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NAFLD NASH Exercise intervention Diet intervention DNA methylation GAB2 Biotechnology TP248.13-248.65 Biology (General) QH301-705.5 Biochemistry QD415-436
spellingShingle	NAFLD NASH Exercise intervention Diet intervention DNA methylation GAB2 Biotechnology TP248.13-248.65 Biology (General) QH301-705.5 Biochemistry QD415-436 Na Wu Fan Yuan Siran Yue Fengyan Jiang Decheng Ren Liangjie Liu Yan Bi Zhenming Guo Lei Ji Ke Han Xiao Yang Mofan Feng Kai Su Fengping Yang Xi Wu Qing Lu Xingwang Li Ruirui Wang Baocheng Liu Shenglong Le Yi Shi Guang He Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
description	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)
format	article
author	Na Wu Fan Yuan Siran Yue Fengyan Jiang Decheng Ren Liangjie Liu Yan Bi Zhenming Guo Lei Ji Ke Han Xiao Yang Mofan Feng Kai Su Fengping Yang Xi Wu Qing Lu Xingwang Li Ruirui Wang Baocheng Liu Shenglong Le Yi Shi Guang He
author_facet	Na Wu Fan Yuan Siran Yue Fengyan Jiang Decheng Ren Liangjie Liu Yan Bi Zhenming Guo Lei Ji Ke Han Xiao Yang Mofan Feng Kai Su Fengping Yang Xi Wu Qing Lu Xingwang Li Ruirui Wang Baocheng Liu Shenglong Le Yi Shi Guang He
author_sort	Na Wu
title	Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
title_short	Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
title_full	Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
title_fullStr	Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
title_full_unstemmed	Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
title_sort	effect of exercise and diet intervention in nafld and nash via gab2 methylation
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ac3f2bdebfae42679d4160c6453e54c4
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Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation

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