GPIHBP1分子与血浆中甘油三酯脂蛋白脂解代谢研究进展

New Insights in GPIHBP1 and the Intravascular Processing of Triglyceride-rich Lipoproteins

脂蛋白酯酶(Lipoprotein lipase,LPL)主要由脂肪和肌肉组织的实质细胞产生,脂解毛细血管中血浆脂蛋白的甘油三酯。多年来,关于LPL是如何从细胞间隙转运至毛细血管内皮细胞上,一直不清楚。最新研究结果表明,在LPL从细胞间隙向毛细血管内皮细胞转运的过程中,糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1(Gly-cosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1,GPIHBP1)发挥着重要的作用。当GPIHBP1缺失时,LPL被错误定位于细胞间隙,导致动物机体出现严重的高甘油三酯血症。Gpihbp1基因突变可致人患高甘油三酯血症。本文就GPIHBP1分子在动物机体健康和疾病状况下的生理作用机理的研究进展进行了综述,同时也对富含甘油三酯脂蛋白脂解代谢中一些尚需解决的问题进行了讨论。

Lipoprotein lipase （LPL） is produced by parenchymal cells from mainly adipocytes and myocytes, but it is involved in hydrolysing triglycerides in plasma lipoproteins at the capillary lumen. For decades, the mechanism by which LPL reaches its site of action in capillaries was unclear, but the problem was recently solved. Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 （GPIHBP1） picks up LPL from the interstitial spaces across endothelial cells to the capillary lumen. When GPIHBP1 is absent, LPL is mislocalized to the interstitial spaces, which lead to severe hypertriglyceridaemia. Some cases of hypertriglyceridaemia in humans are caused by Gpihbp1 mutations that interfere with the ability of GPIHBP1 to bind to LPL. Here, we review recent progress in understanding the role of GPIHBP1 in health and disease and discuss some remaining unresolved issues regarding the processing of triglyceride-rich lipoproteins.