GR-mediated transcriptional regulation of m^(6)A metabolic genes contributes to dietinduced fatty liver in hens  

作　　者：Yue Feng Yanlin Li Wenduo Jiang Yun Hu Yimin Jia Ruqian Zhao 

机构地区：[1]MOE Joint International Research Laboratory of Animal Health&Food Safety,Nanjing Agricultural University,Nanjing,Jiangsu,P.R.China [2]Key Laboratory of Animal Physiology&Biochemistry,College of Veterinary Medicine,Nanjing Agricultural University,Nanjing,Jiangsu,P.R.China

出　　处：《Journal of Animal Science and Biotechnology》2022年第2期488-498,共11页畜牧与生物技术杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (31972638);the National Key Research and Development Program of China (2016YFD0500502);the Fundamental Research Funds for the Central Universities (KYZ201212);the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD);Jiangsu Collaborative Innovation Centre of Meat Production and Processing,Quality and Safety Control。

摘　　要：Background:Glucocorticoid receptor(GR)mediated corticosterone-induced fatty liver syndrome(FLS)in the chicken by transactivation of Fat mass and obesity associated gene(FTO),leading to demethylation of N6-methyladenosine(m^(6)A)and post-transcriptional activation of lipogenic genes.Nutrition is considered the main cause of FLS in the modern poultry industry.Therefore,this study was aimed to investigate whether GR and m^(6)A modification are involved in high-energy and low protein(HELP)diet-induced FLS in laying hens,and if true,what specific m^(6)A sites of lipogenic genes are modified and how GR mediates m^(6)A-dependent lipogenic gene activation in HELP diet-induced FLS in the chicken.Results:Laying hens fed HELP diet exhibit excess(P<0.05)lipid accumulation and lipogenic genes activation in the liver,which is associated with significantly increased(P<0.05)GR expression that coincided with global m^(6)A demethylation.Concurrently,the m^(6)A demethylase FTO is upregulated(P<0.05),whereas the m^(6)A reader YTHDF2 is downregulated(P<0.05)in the liver of FLS chickens.Further analysis identifies site-specific demethylation(P<0.05)of m^(6)A in the mRNA of lipogenic genes,including FASN,SREBP1 and SCD.Moreover,GR binding to the promoter of FTO gene is highly enriched(P<0.05),while GR binding to the promoter of YTHDF2 gene is diminished(P<0.05).Conclusions:These results implicate a possible role of GR-mediated transcriptional regulation of m^(6)A metabolic genes on m^(6)A-depenent post-transcriptional activation of lipogenic genes and shed new light in the molecular mechanism of FLS etiology in the chicken.

关 键 词：Chicken Fatty liver syndrome FTO GR LIPOGENESIS m^(6)A YTHDF2 

分 类 号：S858.31[农业科学—临床兽医学]