摘要
本文综述了载脂蛋白(Apo)A5两大功能:(1) 维持促进甘油三酯正常循环的血浆水平的作用(2)作为肝脂滴组成成分。ApoA5仅在肝脏合成而且循环浓度极低。在血浆中,ApoA5与肝三酰甘油脂蛋白结合,能增强甘油三酯水解和提高残脂蛋白清除率。ApoA5功能丧失与单核苷酸多态性与脂肪分解作用减少、残余间隙低以及并发的高甘油三酯血症有关。尽管在理解ApoA5的病理生理方面取得了实质性的突破,但对细胞内ApoA5蛋白的功能知识十分缺乏。然而,最近的研究表明,细胞内ApoA5 蛋白过度表达与肝细胞中富含甘油三酯脂滴的积累有关。ApoA5可能对非酒精性脂肪性肝病(NAFLD)有着因果作用,因此,ApoA5可作为发治疗非酒精性脂肪性肝病的靶点。
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Current Drug Targets
Title:Apolipoprotein A5: Extracellular and Intracellular Roles in Triglyceride Metabolism
Volume: 16 Issue: 12
Author(s): Trudy M. Forte and Robert O. Ryan
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关键词:
摘要: This review addresses two major functions of apolipoprotein (apo) A5 including (1) its role in maintaining normal plasma levels of circulating triglyceride (TG) and (2) its role as a component of hepatic lipid droplets. ApoA5 is synthesized solely in the liver and circulating concentrations are extremely low. In the plasma, ApoA5 associates with TG-rich lipoproteins and enhances TG hydrolysis and remnant lipoprotein clearance. ApoA5 loss-of-function single nucleotide polymorphisms are associated with reduced lipolysis, poor remnant clearance and concomitantly, hypertriglyceridemia. Although there have been substantial breakthroughs in understanding pathophysiology associated with secreted ApoA5, there is a paucity of knowledge on the functionality of intracellular ApoA5. However, recent studies indicate that overexpression of intracellular ApoA5 is positively associated with accumulation of TG-rich lipid droplets in hepatocytes. It is thought that ApoA5 may have a causal role in non-alcoholic fatty liver disease (NAFLD) and thus, may serve as a target for developing therapeutics for NAFLD.
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Trudy M. Forte and Robert O. Ryan , Apolipoprotein A5: Extracellular and Intracellular Roles in Triglyceride Metabolism, Current Drug Targets 2015; 16 (12) . https://dx.doi.org/10.2174/1389450116666150531161138
DOI https://dx.doi.org/10.2174/1389450116666150531161138 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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