Division of Translational Medicine and Human Genetics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2012;7(2):e31616. doi: 10.1371/journal.pone.0031616. Epub 2012 Feb 20.
Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls.
载脂蛋白 F（apoF）是一种 29 千道尔顿的分泌性唾液糖蛋白，存在于人血浆的高密度脂蛋白（HDL）和低密度脂蛋白（LDL）部分。人类 apoF 也被称为脂质转移抑制剂蛋白（LTIP），因为它能够抑制脂蛋白之间的胆固醇酯转移蛋白（CETP）介导的转移事件。与其他载脂蛋白不同，apoF 被预测缺乏强的两亲性α螺旋，其真正的生理功能仍然未知。我们之前的研究表明，在小鼠中过表达载脂蛋白 F 通过加速从循环中清除，使 HDL 胆固醇水平降低 20-25%。为了研究生理水平的 apoF 表达对 HDL 胆固醇代谢的影响，我们生成了 apoF 缺陷型小鼠。出乎意料的是，apoF 的缺失对血浆脂质浓度、HDL 大小、脂质或蛋白质组成没有实质性影响。在肝胆固醇含量以及血清胆固醇流出能力方面观察到性别特异性差异。在正常饮食条件下，apoF KO 雌性小鼠的肝胆固醇酯含量相对于野生型对照增加（KO：3.4+/-0.9 mg/dl vs. WT：1.2+/-0.3 mg/dl，p<0.05）。在两性中均未观察到 ABCG1 介导的胆固醇流出能力的差异。有趣的是，apoB 耗竭的 KO 雄性小鼠血清在促进 J774 巨噬细胞中 ABCA1 介导的胆固醇流出方面的效果不如 WT 对照。
