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

Title

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

Creator

Xu Y;Li Y;Jadhav K;Pan X;Zhu Y;Hu S;Chen S;Chen L;Tang Y;Wang HH;Yang L;Wang DQ;Yin L;Zhang Y

Publisher

Nature Metabolism

Date

2021
2021-01-18

Description

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 12α-hydroxylase (CYP8B1) in the liver through its interaction with p53 and hepatocyte nuclear factor 4α, respectively. Our data demonstrate that hepatocyte ATF3 is a key regulator of HDL and bile acid metabolism and atherosclerosis.

Format

Journal Article

URL Address

http://doi.org/10.1038/s42255-020-00331-1

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences

Update Year & Number

Jan to Aug list 2021

Citation

Xu Y;Li Y;Jadhav K;Pan X;Zhu Y;Hu S;Chen S;Chen L;Tang Y;Wang HH;Yang L;Wang DQ;Yin L;Zhang Y, “Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism.,” NEOMED Bibliography Database, accessed May 7, 2024, https://neomed.omeka.net/items/show/11853.