Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell Metab. 2010 Jul 7;12(1):42-52. doi: 10.1016/j.cmet.2010.04.016.
The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.
富含甘油三酯的脂蛋白中的甘油三酯经脂蛋白脂肪酶（LPL）的脂解加工是血浆脂质代谢的核心事件，为脂肪组织的脂质储存和心脏等重要器官的燃料供应提供了条件。LPL 由心肌细胞和脂肪细胞合成并分泌，但随后进入毛细血管腔，在那里水解脂蛋白中的甘油三酯。LPL 进入毛细血管腔的机制一直是血浆脂质代谢中悬而未决的问题。在这里，我们表明 GPIHBP1 负责将 LPL 转运到毛细血管中。在 Gpihbp1 缺陷小鼠中，LPL 被错误定位到心肌细胞和脂肪细胞周围的间质空间中。此外，我们还表明 GPIHBP1 位于毛细血管内皮细胞的基底外侧表面，并主动将 LPL 穿过内皮细胞转运。我们的实验定义了 GPIHBP1 在甘油三酯代谢中的功能，并提供了 LPL 进入毛细血管的转运机制。
