Jakel Heidelinde, Nowak Maxime, Helleboid-Chapman Audrey, Fruchart-Najib Jamila, Fruchart Jean-Charles
Département d'Athérosclérose, UR545 INSERM, Université de Lille II, Loos, France.
Ann Med. 2006;38(1):2-10. doi: 10.1080/07853890500407488.
Hypertriglyceridemia is an independent risk factor for the development of cardiovascular disease and is often associated with diabetes, inflammation and the metabolic syndrome. Recently, apolipoprotein A5 (APOA5) was identified as a novel member of the APOA1/C3/A4 gene cluster. Data from mice over-expressing or lacking APOA5 provide direct evidence that this apolipoprotein plays a role in triglyceride metabolism. Moreover, plasma triglyceride levels were found to be strongly associated with APOA5 polymorphisms. The human APOA5 gene is regulated by transcription factors known to affect triglyceride metabolism such as PPARa, RORa, LXR and SREBP-1c and this supports its function. Insulin and interleukins regulate APOA5 gene expression and provide novel clues for the role of this apolipoprotein. To date, the triglyceride lowering action of apoA-V is attributed to the activation of lipoprotein lipase and an acceleration of very low density lipoprotein catabolism. Recent findings indicate that APOA5 could also influence cholesterol homeostasis and probably play a role in hypertriglyceridemia associated with diabetes and inflammation. This review aims to give a comprehensive summary of the current literature and supports the view that APOA5 plays a relevant role in lipid metabolism.
高甘油三酯血症是心血管疾病发生的独立危险因素，且常与糖尿病、炎症及代谢综合征相关。最近，载脂蛋白A5（APOA5）被鉴定为APOA1/C3/A4基因簇的一个新成员。来自过表达或缺乏APOA5的小鼠的数据提供了直接证据，表明这种载脂蛋白在甘油三酯代谢中起作用。此外，发现血浆甘油三酯水平与APOA5基因多态性密切相关。人类APOA5基因受已知影响甘油三酯代谢的转录因子如PPARα、RORα、LXR和SREBP-1c的调控，这支持了其功能。胰岛素和白细胞介素调节APOA5基因表达，并为这种载脂蛋白的作用提供了新线索。迄今为止，载脂蛋白A-V的降甘油三酯作用归因于脂蛋白脂肪酶的激活和极低密度脂蛋白分解代谢的加速。最近的研究结果表明，APOA5也可能影响胆固醇稳态，并且可能在与糖尿病和炎症相关的高甘油三酯血症中起作用。这篇综述旨在对当前文献进行全面总结，并支持APOA5在脂质代谢中起相关作用的观点。
