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花生四烯酸代谢与肝脏糖脂代谢稳态调控

李沙¹, 苏文², 张晓燕³, 管又飞^4,*

¹河北工程大学医学院，邯郸 056038；²深圳大学医学院，深圳 518060；³华东师范大学医学与健康研究院，上海 200241；⁴大连医科大学医学科学研究院，大连 116044

摘要

花生四烯酸(arachidonic acid, AA)是一种ω-6多不饱和脂肪酸，在生物体内主要是以磷脂的形式存在于细胞膜上。AA在细胞内主要通过环氧合酶(cyclooxygenase, COX)途径、脂氧合酶(lipoxygenases, LOX)途径、细胞色素P450单氧化酶(cytochrome P450 monooxygenase, CYP450)途径等进行代谢。糖脂代谢的稳态调控是维持机体基本生命活动的基础，肝脏是糖脂代谢调控的中枢器官。肝脏糖脂代谢紊乱与2型糖尿病、非酒精性脂肪性肝病等代谢性疾病的发生和发展密切相关。已有研究表明AA代谢与肝脏糖脂代谢紊乱有密切的关系。本文就AA代谢在肝脏糖脂代谢稳态调控中的作用及其作为脂肪肝和胰岛素抵抗等代谢性疾病治疗靶点的价值作一综述。

关键词： 花生四烯酸; 肝脏; 代谢; 脂质介质; 代谢性疾病

分类号：Q493.4;Q493.5;Q493.9

Arachidonic acid metabolism in liver glucose and lipid homeostasis

LI Sha¹, SU Wen², ZHANG Xiao-Yan³, GUAN You-Fei^4,*

¹Medical College, Hebei University of Engineering, Handan 056038, China；²Health Science Center, Shenzhen University, Shenzhen 518060, China；³Health Science Center, East China Normal University, Shanghai 200241, China；⁴Advanced Institute of Medical Science, Dalian Medical University, Dalian 116044, China

Abstract

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and non- alcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.

Key words: arachidonic acid; liver; metabolism; lipid mediator; metabolic diseases

收稿日期：2021-02-25　　录用日期：2021-04-08

通讯作者：管又飞　　E-mail: guanyf@dmu.edu.cn

DOI: 10.13294/j.aps.2021.0052

引用本文：

李沙, 苏文, 张晓燕, 管又飞. 花生四烯酸代谢与肝脏糖脂代谢稳态调控[J]. 生理学报 2021; 73 (4): 657-664.

LI Sha, SU Wen, ZHANG Xiao-Yan, GUAN You-Fei. Arachidonic acid metabolism in liver glucose and lipid homeostasis. Acta Physiol Sin 2021; 73 (4): 657-664 (in Chinese with English abstract).