Kim Jong-Won, Kim Yu Ji
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical School, Jeonbuk National University, Research Institute of Clinical Medicine of Jeonbuk National University - Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.
Pharmacology. 2024;109(6):305-311. doi: 10.1159/000540351. Epub 2024 Jul 22.
Cholesterol homeostasis in the human body is a crucial process that involves a delicate balance between dietary cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver. Both pathways contribute significantly to the overall pool of cholesterol in the body, influencing plasma cholesterol levels and impacting cardiovascular health. Elevated absorption of cholesterol in the intestines has a suppressive impact on the synthesis of cholesterol in the liver, serving to preserve cholesterol balance. Nonetheless, the precise mechanisms driving this phenomenon remain largely unclear.
This review aimed to discuss the previously unrecognized role of cholesin and GPR146 in the regulation of cholesterol biosynthesis, providing a novel conceptual framework for understanding cholesterol homeostasis.
The discovery of cholesin, a novel protein implicated in the regulation of cholesterol homeostasis, represents a significant advancement in our understanding of cholesterol biosynthesis and its associated pathways. The cholesin-GPR146 axis could have profound implications across various therapeutic areas concerning abnormal cholesterol metabolism, offering new hope for patients and improving overall healthcare outcomes.
人体中的胆固醇稳态是一个关键过程，涉及肠道中膳食胆固醇吸收与肝脏中胆固醇从头合成之间的微妙平衡。这两条途径对体内胆固醇的总量都有显著贡献，影响血浆胆固醇水平并对心血管健康产生影响。肠道中胆固醇吸收的增加对肝脏中胆固醇的合成具有抑制作用，有助于维持胆固醇平衡。然而，驱动这一现象的确切机制在很大程度上仍不清楚。
本综述旨在讨论胆甾醇和GPR146在胆固醇生物合成调节中以前未被认识的作用，为理解胆固醇稳态提供一个新的概念框架。
胆甾醇的发现，一种与胆固醇稳态调节有关的新型蛋白质，代表了我们对胆固醇生物合成及其相关途径理解的重大进展。胆甾醇 - GPR146轴可能在涉及异常胆固醇代谢的各个治疗领域产生深远影响，为患者带来新希望并改善整体医疗结果。
