Heimerl Susanne, Liebisch Gerhard, Le Lay Soazig, Böttcher Alfred, Wiesner Philipp, Lindtner Silke, Kurzchalia Teymuras V, Simons Kai, Schmitz Gerd
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.
Biochem Biophys Res Commun. 2008 Mar 21;367(4):826-33. doi: 10.1016/j.bbrc.2008.01.010. Epub 2008 Jan 10.
Caveolae are specialized membrane microdomains formed as the result of local accumulation of cholesterol, glycosphingolipids, and the structural protein caveolin-1 (Cav-1). To further elucidate the role of Cav-1 in lipid homeostasis in-vivo, we analyzed fasting and post-prandial plasma from Cav-1 deficient mice on low or on high fat diet. In total plasma analysis, an increase in ceramide and hexosylceramide was observed. In cholesteryl ester (CE), we found an increased saturated+monounsaturated/polyunsaturated fatty acid ratio in fasting plasma of low fat fed Cav-1(-/-) mice with increased proportions of CE16:1, CE18:1, CE20:3, and decreased proportions of CE18:2 and CE22:6. Under high fat diet HDL-CE, free cholesterol and pre-beta-HDL were increased accompanied by a shift from slow to fast migrating alpha-HDL and expansion of apoE containing HDL. Our results demonstrate a significant role of Cav-1 in HDL-cholesterol metabolism and may reflect a variety of Cav-1 functions including modulation of ACAT activity and SR-BI function.
小窝是由胆固醇、糖鞘脂和结构蛋白小窝蛋白-1(Cav-1)局部聚集形成的特殊膜微区。为了进一步阐明Cav-1在体内脂质稳态中的作用,我们分析了低脂或高脂饮食的Cav-1缺陷小鼠的空腹和餐后血浆。在总血浆分析中,观察到神经酰胺和己糖神经酰胺增加。在胆固醇酯(CE)方面,我们发现低脂喂养的Cav-1(-/-)小鼠空腹血浆中饱和+单不饱和/多不饱和脂肪酸比值增加,CE16:1、CE18:1、CE20:3的比例增加,而CE18:2和CE22:6的比例降低。在高脂饮食下,HDL-CE、游离胆固醇和前β-HDL增加,同时伴随着α-HDL从慢速迁移向快速迁移的转变以及含载脂蛋白E的HDL的扩展。我们的结果表明Cav-1在HDL胆固醇代谢中起重要作用,可能反映了Cav-1的多种功能,包括对ACAT活性和SR-BI功能的调节。