Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function

脂肪变性 脂肪肝 脂肪性肝炎 基因敲除 生物 自噬 肝细胞 线粒体 脂质代谢 β氧化 内科学 内分泌学 肉碱 医学 生物化学 新陈代谢 疾病 基因 细胞凋亡 体外
作者
Natália da Silva Lima,Marcos F. Fondevila,Eva María Novoa,Xabier Buqué,María Mercado-Gómez,Sarah Gallet,María J. Gonzalez-Rellan,Uxia Fernandez,Anne Loyens,María García-Vence,María Pilar Chantada–Vázquez,Susana B. Bravo,Patricia Marañón,Ana Senra,Adriana Escudero,Magdalena Leiva,Diana Guallar,Miguel Fidalgo,Pedro Gomes,Marc Claret,Guadalupe Sabio,Marta Varela–Rey,Teresa C. Delgado,Rocío Montero‐Vallejo,Javier Ampuero,Miguel López,Carlos Diéguez,Laura Herrero,Dolors Serra,Markus Schwaninger,Vincent Prévot,Rocío Gallego‐Durán,Manuel Romero‐Gómez,Paula Iruzubieta,Javier Crespo,María Luz Martínez‐Chantar,Carmelo García‐Monzón,Águeda González‐Rodríguez,Patricia Aspichueta,Rubén Nogueiras
出处
期刊:Journal of Hepatology [Elsevier]
卷期号:76 (1): 11-24 被引量:17
标识
DOI:10.1016/j.jhep.2021.09.008
摘要

Autophagy-related gene 3 (ATG3) is an enzyme mainly known for its actions in the LC3 lipidation process, which is essential for autophagy. Whether ATG3 plays a role in lipid metabolism or contributes to non-alcoholic fatty liver disease (NAFLD) remains unknown.By performing proteomic analysis on livers from mice with genetic manipulation of hepatic p63, a regulator of fatty acid metabolism, we identified ATG3 as a new target downstream of p63. ATG3 was evaluated in liver samples from patients with NAFLD. Further, genetic manipulation of ATG3 was performed in human hepatocyte cell lines, primary hepatocytes and in the livers of mice.ATG3 expression is induced in the liver of animal models and patients with NAFLD (both steatosis and non-alcoholic steatohepatitis) compared with those without liver disease. Moreover, genetic knockdown of ATG3 in mice and human hepatocytes ameliorates p63- and diet-induced steatosis, while its overexpression increases the lipid load in hepatocytes. The inhibition of hepatic ATG3 improves fatty acid metabolism by reducing c-Jun N-terminal protein kinase 1 (JNK1), which increases sirtuin 1 (SIRT1), carnitine palmitoyltransferase 1a (CPT1a), and mitochondrial function. Hepatic knockdown of SIRT1 and CPT1a blunts the effects of ATG3 on mitochondrial activity. Unexpectedly, these effects are independent of an autophagic action.Collectively, these findings indicate that ATG3 is a novel protein implicated in the development of steatosis.We show that autophagy-related gene 3 (ATG3) contributes to the progression of non-alcoholic fatty liver disease in humans and mice. Hepatic knockdown of ATG3 ameliorates the development of NAFLD by stimulating mitochondrial function. Thus, ATG3 is an important factor implicated in steatosis.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
echoanne关注了科研通微信公众号
刚刚
3秒前
Winter完成签到 ,获得积分10
4秒前
上官若男应助祭酒采纳,获得10
5秒前
小可爱完成签到,获得积分10
5秒前
benben应助勤劳曼寒采纳,获得10
6秒前
DraGon完成签到,获得积分10
6秒前
xzz完成签到,获得积分10
7秒前
积极白梦发布了新的文献求助10
7秒前
zhang0403完成签到,获得积分10
7秒前
8秒前
huan完成签到,获得积分10
10秒前
2123121321321完成签到 ,获得积分10
13秒前
wjh完成签到 ,获得积分10
13秒前
小研发布了新的文献求助20
14秒前
15秒前
yongzaizhuigan完成签到,获得积分10
15秒前
SX0000完成签到 ,获得积分20
17秒前
Allen完成签到,获得积分10
17秒前
18秒前
小梦完成签到,获得积分10
18秒前
机灵的千琴完成签到,获得积分10
20秒前
Jim完成签到,获得积分10
21秒前
隐形曼青应助刘海鸥采纳,获得20
21秒前
传奇3应助Sience采纳,获得10
22秒前
老衲完成签到,获得积分10
22秒前
平者完成签到,获得积分10
22秒前
打打应助小小怪采纳,获得10
22秒前
23秒前
23秒前
百汇科研完成签到,获得积分10
25秒前
26秒前
echoanne发布了新的文献求助10
28秒前
万能图书馆应助qingzhou采纳,获得10
29秒前
JamesPei应助hhhhh采纳,获得10
29秒前
安详的岩发布了新的文献求助10
29秒前
31秒前
Ting完成签到,获得积分10
34秒前
pyf不懂科研完成签到,获得积分10
34秒前
fan051500完成签到,获得积分10
35秒前
高分求助中
Teaching Social and Emotional Learning in Physical Education 900
Plesiosaur extinction cycles; events that mark the beginning, middle and end of the Cretaceous 800
Recherches Ethnographiques sue les Yao dans la Chine du Sud 500
Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism 500
Chinese-English Translation Lexicon Version 3.0 500
Wisdom, Gods and Literature Studies in Assyriology in Honour of W. G. Lambert 400
薩提亞模式團體方案對青年情侶輔導效果之研究 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 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 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2391823
求助须知:如何正确求助?哪些是违规求助? 2096649
关于积分的说明 5281811
捐赠科研通 1824208
什么是DOI,文献DOI怎么找? 909793
版权声明 559864
科研通“疑难数据库(出版商)”最低求助积分说明 486146