Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism

doi:10.1038/s42255-020-00331-1

	Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism
	Xu, Yanyong 2; Li, Yuanyuan 2,6,7; Jadhav, Kavita 2; Pan, Xiaoli 2,3; Zhu, Yingdong 2; Hu, Shuwei 2; Chen, Shaoru 2; Chen, Liuying 3; Tang, Yong 4; Wang, Helen H.1,5
刊名	NATURE METABOLISM
	2021-01-18
页码	31
DOI	10.1038/s42255-020-00331-1
通讯作者	Zhang, Yanqiao(yzhang@neomed.edu)
英文摘要	Activating transcription factor (ATF)3 is known to have an anti-inflammatory function, yet the role of hepatic ATF3 in lipoprotein metabolism or atherosclerosis remains unknown. Here we show that overexpression of human ATF3 in hepatocytes reduces the development of atherosclerosis in Western-diet-fed Ldlr(-/-) or Apoe(-/-) mice, whereas hepatocyte-specific ablation of Atf3 has the opposite effect. We further show that hepatic ATF3 expression is inhibited by hydrocortisone. Mechanistically, hepatocyte ATF3 enhances high-density lipoprotein (HDL) uptake, inhibits intestinal fat and cholesterol absorption and promotes macrophage reverse cholesterol transport by inducing scavenger receptor group B type 1 (SR-BI) and repressing cholesterol 12 alpha-hydroxylase (CYP8B1) in the liver through its interaction with p53 and hepatocyte nuclear factor 4 alpha, respectively. Our data demonstrate that hepatocyte ATF3 is a key regulator of HDL and bile acid metabolism and atherosclerosis. Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism.
资助项目	National Institutes of Health[R01DK102619] ; National Institutes of Health[R01HL103227] ; National Institutes of Health[R01HL142086] ; National Institutes of Health[R01DK118941] ; National Institutes of Health[R01DK118805]
WOS关键词	REVERSE CHOLESTEROL TRANSPORT ; HIGH-DENSITY-LIPOPROTEIN ; ACTIVATING TRANSCRIPTION FACTOR-3 ; DUAL-RELEASE HYDROCORTISONE ; CORONARY-ARTERY-DISEASE ; RECEPTOR-DEFICIENT MICE ; SR-BI ; ADRENAL INSUFFICIENCY ; PREVENTS ATHEROSCLEROSIS ; URSODEOXYCHOLIC ACID
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000610413900006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/295975]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Yanqiao
作者单位	1.Albert Einstein Coll Med, Bronx, NY 10467 USA 2.Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH 44272 USA 3.Huazhong Univ Sci & Technol, Union Hosp, Div Gastroenterol, Tongji Med Coll, Wuhan, Peoples R China 4.Huazhong Univ Sci & Technol, Union Hosp, Dept Hepatobiliary Surg, Tongji Med Coll, Wuhan, Peoples R China 5.Marion Bessin Liver Res Ctr, Dept Med & Genet, Bronx, NY USA 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 7.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Inst Drug Discovery, Zhongshan, Peoples R China
推荐引用方式 GB/T 7714	Xu, Yanyong,Li, Yuanyuan,Jadhav, Kavita,et al. Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism[J]. NATURE METABOLISM,2021:31.
APA	Xu, Yanyong.,Li, Yuanyuan.,Jadhav, Kavita.,Pan, Xiaoli.,Zhu, Yingdong.,...&Zhang, Yanqiao.(2021).Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism.NATURE METABOLISM,31.
MLA	Xu, Yanyong,et al."Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism".NATURE METABOLISM (2021):31.