铜蓝蛋白在脂质代谢稳态调控中作用的研究进展

doi:10.3969/j.issn.1674-8115.2024.01.014

摘要/Abstract

摘要：

血浆铜蓝蛋白（ceruloplasmin，Cp）是肝脏分泌的重要蛋白质，在人体的铜离子分布和运输中扮演关键角色，并在维持铜离子稳态方面起重要作用。此外，Cp还是一种亚铁氧化酶，参与人体内铁离子的代谢。研究表明，Cp与糖尿病和心血管疾病等代谢相关疾病有密切关系。近来研究发现，Cp也参与脂质代谢的调控过程。脂质代谢平衡涉及体内脂质合成、脂肪水解、脂肪酸氧化、脂质运输和吸收等过程。脂质代谢紊乱会导致人体代谢紊乱和心血管并发症的发生。Cp通过多种方式调控脂质代谢。一方面，它通过亚铁氧化酶活性参与调节氧化应激，即在铁代谢和氧化还原反应中发挥作用。另一方面，它通过铜及含铜的代谢酶参与胆固醇、脂蛋白和脂肪酸等物质代谢过程的调控。因此，Cp通过影响铜或铁依赖性酶和相关通路在铜和铁的稳态中发挥作用进而调控脂质代谢。尽管已经发现Cp与脂质代谢密切关联的现象，但仍需要进一步研究Cp进行脂质代谢调控的确切机制。该综述总结了Cp在脂质代谢中的作用及其研究进展，以期为脂质代谢紊乱相关疾病的研究和治疗提供新的思路。

关键词: 铜蓝蛋白, 铜稳态, 铁稳态, 脂质代谢, 代谢性疾病

Abstract:

Ceruloplasmin (Cp) is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body, thereby maintaining copper homeostasis. Additionally, Cp functions as a significant enzyme known as ferroxidase, which is involved in iron metabolism within the body. Numerous studies have suggested a close relationship between Cp and metabolic disorders, such as diabetes and cardiovascular diseases. Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism. The various activities associated with lipid metabolism, including lipid synthesis, adipose hydrolysis, fatty acid oxidation, lipid transport, and absorption, collectively contribute to maintaining lipid homeostasis. Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications. Cp regulates lipid metabolism through two main mechanisms. Firstly, Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction. Secondly, copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism, lipoprotein metabolism, and fatty acid synthesis. As a result, the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways. Although the correlation between Cp and lipid metabolism has been identified, an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted. This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research, with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

Key words: ceruloplasmin, copper homeostasis, iron homeostasis, lipid metabolism, metabolic disease

中图分类号:

R589.2

江全鑫, 陈素贞, 刘军力. 铜蓝蛋白在脂质代谢稳态调控中作用的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(1): 124-130.

JIANG Quanxin, CHEN Suzhen, LIU Junli. Research progress in ceruloplasmin regulation of lipid metabolism homeostasis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(1): 124-130.

图/表 2

图1 Cp的晶体结构

Fig 1 Crystal structure of Cp

图2 肝脏中Cp调控脂质代谢示意图Note： STEAP—six-transmembrane epithelial antigen of prostate; Cp—ceruloplasmin; Ctr1—copper transporter 1; ATP7A—ATP-dependent copper transporter 7A; Atox1—antioxidant 1; SCO1—synthesis of cytochrome C oxidase 1; AMPKα—AMP-activated protein kinase-α; LKB1—liver kinase B1; ATP7B—ATP-dependent copper transporter 7B; TGN—trans-Golgi network; ROS—reactive oxygen species; FAO—fatty acid oxidation; PGC1α— peroxisome proliferator-activated receptor-γ coactivator-1α.

Fig 2 Schematic diagram of Cp regulation of lipid metabolism in the liver

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