A gut-derived hormone regulates cholesterol metabolism

被引：37

作者：

Hu, Xiaoli ^{[1
]}

Chen, Fengyi ^{[1
]}

Jia, Liangjie ^{[1
]}

Long, Aijun ^{[1
]}

Peng, Ying ^{[1
]}

Li, Xu ^{[2
]}

Huang, Junfeng ^{[2
]}

Wei, Xueyun ^{[2
]}

Fang, Xinlei ^{[1
]}

Gao, Zihua ^{[1
]}

Zhang, Mengxian ^{[1
]}

Liu, Xiao ^{[3
]}

Chen, Ye-Guang ^{[1
,4
,5
]}

Wang, Yan ^{[3
]}

Zhang, Huijie ^{[2
]}

Wang, Yiguo ^{[1
]}

机构：

[1] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Sch Life Sci, State Key Lab Membrane Biol,MOE,Key Lab Bioinforma, Beijing 100084, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Endocrinol & Metab, Guangzhou 510515, Peoples R China

[3] Wuhan Univ, Coll Life Sci, TaiKang Ctr Life & Med Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China

[4] Guangzhou Lab, Guangzhou 510005, Peoples R China

[5] Nanchang Univ, Jiangxi Med Coll, Sch Basic Med Sci, Nanchang 330031, Peoples R China

来源：

CELL | 2024年 / 187卷 / 07期

基金：

中国国家自然科学基金;

关键词：

ELEMENT-BINDING PROTEINS; DENSITY-LIPOPROTEIN CHOLESTEROL; HMG-COA REDUCTASE; DIETARY-CHOLESTEROL; LIPID-METABOLISM; PLASMA-LIPIDS; ABSORPTION; EZETIMIBE; MECHANISMS; INHIBITION;

D O I：

10.1016/j.cell.2024.02.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The reciprocal coordination between cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver is essential for maintaining cholesterol homeostasis, yet the mechanisms governing the opposing regulation of these processes remain poorly understood. Here, we identify a hormone, Cholesin, which is capable of inhibiting cholesterol synthesis in the liver, leading to a reduction in circulating cholesterol levels. Cholesin is encoded by a gene with a previously unknown function ( C7orf50 in humans; 3110082I17Rik in mice). It is secreted from the intestine in response to cholesterol absorption and binds to GPR146, an orphan G -protein -coupled receptor, exerting antagonistic downstream effects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterol synthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effective agent in combating hypercholesterolemia and atherosclerosis.

引用

页码：1685 / 1700.e18

页数：35

共 77 条

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