清华大学Yiguo Wang和南方医科大学Huijie Zhang共同合作，近期取得重要工作进展。他们研究提出了一种肠源激素（Cholesin）对胆固醇代谢的调控作用。相关研究成果2024年3月18日在线发表于《细胞》杂志上。

据介绍，肠道中的胆固醇吸收和肝脏中的从头胆固醇合成之间的相互协调对于维持胆固醇稳态至关重要，但对这些过程的相反调节机制仍知之甚少。

研究人员发现了一种叫做Cholesin（肠抑脂素）的肠道激素，它能够抑制肝脏中的胆固醇合成，从而降低循环胆固醇水平。Cholesin由一种以前未知功能的基因编码（人类中为C7orf50；小鼠中为3110082I17Rik）。它由肠道分泌以响应胆固醇吸收，并与GPR146（一种孤儿G蛋白偶联受体）结合，通过抑制PKA信号传导发挥拮抗下游作用，从而抑制肝脏中SREBP2控制的胆固醇合成。

因此，这一研究结果表明，Cholesin-GPR146轴介导了肠道胆固醇吸收对肝脏胆固醇合成的抑制作用。Cholesin有望成为对抗高胆固醇血症和动脉粥样硬化的有效药物。

附：英文原文

Title: A gut-derived hormone regulates cholesterol metabolism

Author: Xiaoli Hu, Fengyi Chen, Liangjie Jia, Aijun Long, Ying Peng, Xu Li, Junfeng Huang, Xueyun Wei, Xinlei Fang, Zihua Gao, Mengxian Zhang, Xiao Liu, Ye-Guang Chen, Yan Wang, Huijie Zhang, Yiguo Wang

Issue&Volume: 2024-03-18

Abstract: 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 poorlyunderstood. Here, we identify a hormone, Cholesin, which is capable of inhibitingcholesterol synthesis in the liver, leading to a reduction in circulating cholesterollevels. 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 absorptionand binds to GPR146, an orphan G-protein-coupled receptor, exerting antagonistic downstreameffects by inhibiting PKA signaling and thereby suppressing SREBP2-controlled cholesterolsynthesis in the liver. Therefore, our results demonstrate that the Cholesin-GPR146axis mediates the inhibitory effect of intestinal cholesterol absorption on hepaticcholesterol synthesis. This discovered hormone, Cholesin, holds promise as an effectiveagent in combating hypercholesterolemia and atherosclerosis.

DOI: 10.1016/j.cell.2024.02.024

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00226-5