Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels

乙酰化 PCAF公司 表观基因组 组蛋白 组蛋白乙酰转移酶 生物 组蛋白乙酰转移酶 生物化学 基因表达 基因 DNA甲基化
作者
Alessandro Carrer,Joshua L.D. Parris,Sophie Trefely,Ryan A. Henry,David C. Montgomery,Ann M. Torres,John M. Viola,Yin‐Ming Kuo,Ian A. Blair,Jordan L. Meier,Andrew J. Andrews,Nathaniel W. Snyder,Kathryn E. Wellen
出处
期刊:Journal of Biological Chemistry [Elsevier BV]
卷期号:292 (8): 3312-3322 被引量:141
标识
DOI:10.1074/jbc.m116.750620
摘要

Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that mice consuming a HFD have reduced levels of acetyl-CoA and/or acetyl-CoA:CoA ratio in these tissues. In WAT and the pancreas, HFD also impacted the levels of histone acetylation; in particular, histone H3 lysine 23 acetylation was lower in HFD-fed mice. Genetic deletion of Acly in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In the liver, no significant effects on histone acetylation were observed with a HFD despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase P300/CBP-associated factor (PCAF) in liver lysates and inhibited its activity in vitro. This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in the liver. Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that mice consuming a HFD have reduced levels of acetyl-CoA and/or acetyl-CoA:CoA ratio in these tissues. In WAT and the pancreas, HFD also impacted the levels of histone acetylation; in particular, histone H3 lysine 23 acetylation was lower in HFD-fed mice. Genetic deletion of Acly in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In the liver, no significant effects on histone acetylation were observed with a HFD despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase P300/CBP-associated factor (PCAF) in liver lysates and inhibited its activity in vitro. This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in the liver.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
科目三应助糊涂的猎豹采纳,获得10
1秒前
2秒前
风清扬应助清脆的灵煌采纳,获得30
2秒前
思源应助美好斓采纳,获得30
4秒前
成功应助hkh采纳,获得10
4秒前
酷波er应助信仰阳光快乐采纳,获得10
5秒前
Tong完成签到,获得积分10
6秒前
香蕉觅云应助克林沙星采纳,获得10
6秒前
田様应助孙成成采纳,获得10
6秒前
一把过发布了新的文献求助10
7秒前
新嘟发布了新的文献求助10
8秒前
Owen应助12采纳,获得10
9秒前
9秒前
9秒前
12秒前
开朗艳一发布了新的文献求助10
14秒前
Emily完成签到,获得积分10
14秒前
16秒前
量子星尘发布了新的文献求助10
16秒前
沉静乌龟发布了新的文献求助10
18秒前
18秒前
18秒前
19秒前
mia发布了新的文献求助20
21秒前
木乙完成签到 ,获得积分10
21秒前
21秒前
SYLH应助开朗艳一采纳,获得10
22秒前
务实的寻凝完成签到 ,获得积分10
24秒前
25秒前
Mia发布了新的文献求助30
27秒前
彭剑封发布了新的文献求助10
27秒前
pazhao完成签到,获得积分10
28秒前
冬1发布了新的文献求助10
28秒前
军帽完成签到,获得积分20
30秒前
小蘑菇应助新嘟采纳,获得10
31秒前
31秒前
111完成签到,获得积分20
32秒前
Emily发布了新的文献求助10
32秒前
32秒前
33秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975610
求助须知:如何正确求助?哪些是违规求助? 3519986
关于积分的说明 11200337
捐赠科研通 3256337
什么是DOI,文献DOI怎么找? 1798246
邀请新用户注册赠送积分活动 877446
科研通“疑难数据库(出版商)”最低求助积分说明 806357