From the Department of Cell Biology, State University of New York, Downstate Medical Center, Brooklyn (H.J., A.Y., Y.C., X.Z., R.L., Z.L., W.J., X.C.J.); Fudan University, Shanghai, China (B.L., Y.C.); Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, New York (Z.L., X.C.J); Institute of Atherosclerosis, Taishan Medical University, Taian, China (X.Z., S.Q.); Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (H.H.B., M.S.K.); and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA (M.N.).
Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):316-22. doi: 10.1161/ATVBAHA.114.303764. Epub 2014 Dec 4.
Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined.
We crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre recombinase (Cre) transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cre mice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%), high-density lipoprotein-cholesterol (21%), high-density lipoprotein-phospholipid (20%), and apolipoprotein A-I (33%) levels, but had no effect on nonhigh-density lipoprotein levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cre mice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type→PLTP-Flox-ΔNeo/aP2-Cre and wild-type→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (wild-type→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apolipoprotein A-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apolipoprotein A-I and high-density lipoprotein lipids, we measured apolipoprotein A-I-mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants.
Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.
磷脂转运蛋白（PLTP）在脂肪组织中高度表达。因此，研究了脂肪组织 PLTP 对血浆脂蛋白代谢的影响。
我们将 PLTP-Flox-ΔNeo 和脂肪细胞蛋白 2（aP2）-Cre 重组酶（Cre）转基因小鼠进行杂交，创建了 PLTP-Flox-ΔNeo/aP2-Cre 小鼠，其脂肪组织和巨噬细胞中的 PLTP mRNA 分别减少了 90%和 60%。PLTP 缺失导致血浆 PLTP 活性（22%）、高密度脂蛋白胆固醇（21%）、高密度脂蛋白磷脂（20%）和载脂蛋白 A-I（33%）水平显著降低，但与 PLTP-Flox-ΔNeo 对照组相比，对非高密度脂蛋白水平没有影响。为了消除巨噬细胞中 PLTP 缺失的可能影响，我们对 PLTP-Flox-ΔNeo/aP2-Cre 小鼠和 PLTP-Flox-ΔNeo 小鼠进行致死性辐射，并将野生型小鼠骨髓移植到其中，创建了野生型→PLTP-Flox-ΔNeo/aP2-Cre 和野生型→PLTP-Flox-ΔNeo 小鼠。因此，我们构建了一种脂肪细胞中缺乏 PLTP 但不缺乏巨噬细胞的小鼠模型（野生型→PLTP-Flox-ΔNeo/aP2-Cre）。这些敲除小鼠的血浆 PLTP 活性（19%）、胆固醇（18%）、磷脂（17%）和载脂蛋白 A-I（26%）水平也显著降低。为了进一步研究血浆载脂蛋白 A-I 和高密度脂蛋白脂质减少的机制，我们测量了脂肪组织外植体中载脂蛋白 A-I 介导的胆固醇流出，发现内源性和外源性 PLTP 显著增加了外植体中的胆固醇流出。
脂肪细胞 PLTP 在血浆 PLTP 活性中发挥了较小但显著的作用，并促进了胆固醇从脂肪组织中的流出。
