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首页> 外文期刊>Current opinion in lipidology >The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism?
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The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism?

机译：载脂蛋白CIII和AV的作用和作用方式：甘油三酸酯代谢中的协同作用因子？

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PURPOSE OF REVIEW: Apolipoprotein (apo)CIII and apoAV play an important role in triglyceride metabolism as evidenced by the unambiguous and opposing phenotypes of transgenic and knockout mouse models. In this review we discuss studies on the genetics, protein structure, and regulation of apoCIII and apoAV and compare their potential molecular mechanisms of action in triglyceride metabolism. We examine the hypothesis that apoCIII and apoAV synergistically affect triglyceride metabolism. RECENT FINDINGS: It has now been firmly established that variation in plasma triglyceride levels in a wide range of human populations is strongly associated with genetic variation at the chromosomal locus encoding both the APOC3 and APOA5 genes, the APOA1/C3/A4/A5 gene cluster. The close physical linkage of these genes and the frequent concurrence of genetic variants, however, complicate the assignment of specific metabolic defects to specific polymorphisms. Recent insight into the regulation of APOC3 and APOA5 gene expression and structural modeling studies on the apoAV protein have provided novel clues for the potential molecular mechanisms responsible for the effects of apoCIII and apoAV on triglyceride metabolism. SUMMARY: Hypertriglyceridemia is a major independent risk factor in the development of cardiovascular disease. Moreover, triglyceride-derived fatty acids are thought to play a key role in the development and progression of the metabolic syndrome. As modulators of triglyceride metabolism, apoCIII and apoAV are key players and potential therapeutic targets. However, little is known of their molecular mechanism and potential cooperativity. Rational therapeutic application will require the filling of this hiatus in our knowledge.
机译：审查的目的：载脂蛋白（apo）CIII和apoAV在甘油三酸酯代谢中起重要作用，转基因和敲除小鼠模型的明确和相反的表型证明了这一点。在这篇综述中，我们讨论了关于apoCIII和apoAV的遗传学，蛋白质结构和调控的研究，并比较了它们在甘油三酸酯代谢中的潜在分子机制。我们检查了载脂蛋白CIII和载脂蛋白AV协同影响甘油三酸酯代谢的假说。最近的发现：现已牢固地确定，在广泛的人群中血浆甘油三酸酯水平的变化与编码APOC3和APOA5基因，APOA1 / C3 / A4 / A5基因簇的染色体基因座的遗传变化密切相关。 。这些基因的紧密物理联系以及遗传变异的频繁并发使特定代谢缺陷与特定多态性的分配变得复杂。最近对APOC3和APOA5基因表达的调控以及对apoAV蛋白的结构建模研究的新见解为负责apoCIII和apoAV对甘油三酸酯代谢的潜在分子机制提供了新线索。摘要：高甘油三酯血症是心血管疾病发展中的主要独立危险因素。此外，甘油三酸酯衍生的脂肪酸被认为在代谢综合征的发生和发展中起关键作用。作为甘油三酸酯代谢的调节剂，apoCIII和apoAV是关键角色和潜在的治疗靶标。但是，对其分子机理和潜在的协同作用知之甚少。合理的治疗应用将需要填补我们所学知识的空白。

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