Department of Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
J Lipid Res. 2013 Apr;54(4):1124-34. doi: 10.1194/jlr.M035568. Epub 2013 Feb 3.
The role of macrophage lipoprotein lipase (LpL) in the development of atherosclerosis and adiposity was examined in macrophage LpL knockout (MLpLKO) mice. MLpLKO mice were generated using cre-loxP gene targeting. Loss of LpL in macrophages did not alter plasma LpL activity or lipoprotein levels. Incubation of apolipoprotein E (ApoE)-deficient β-VLDL with peritoneal macrophages from ApoE knockout mice lacking macrophage LpL (MLpLKO/ApoEKO) led to less cholesteryl ester formation than that found with ApoEKO macrophages. MLpLKO/ApoEKO macrophages had reduced intracellular triglyceride levels, with decreased CD36 and carnitine palmitoyltransferase-1 mRNA levels compared with ApoEKO macrophages, when incubated with VLDL. Although both MLpLKO/ApoEKO and ApoEKO mice developed comparable hypercholesterolemia in response to feeding with a Western-type diet for 12 weeks, atherosclerosis was less in MLpLKO/ApoEKO mice. Epididymal fat mass and gene expression levels associated with inflammation did not differ between the two groups. In conclusion, macrophage LpL plays an important role in the development of atherosclerosis but not adiposity.
研究了巨噬细胞脂蛋白脂肪酶（LpL）在动脉粥样硬化和肥胖发展中的作用，在巨噬细胞 LpL 敲除（MLpLKO）小鼠中进行了研究。使用 cre-loxP 基因靶向技术生成了 MLpLKO 小鼠。巨噬细胞中 LpL 的缺失并未改变血浆 LpL 活性或脂蛋白水平。用载脂蛋白 E（ApoE）缺陷的β-VLDL 孵育缺乏巨噬细胞 LpL（MLpLKO/ApoEKO）的 ApoE 敲除小鼠的腹腔巨噬细胞，导致胆固醇酯形成比 ApoEKO 巨噬细胞少。与 ApoEKO 巨噬细胞相比，用 VLDL 孵育时，MLpLKO/ApoEKO 巨噬细胞的细胞内甘油三酯水平降低，CD36 和肉碱棕榈酰转移酶-1 mRNA 水平降低。尽管 MLpLKO/ApoEKO 和 ApoEKO 小鼠在用西方饮食喂养 12 周后均发生类似的高胆固醇血症，但 MLpLKO/ApoEKO 小鼠的动脉粥样硬化程度较低。两组之间的附睾脂肪量和与炎症相关的基因表达水平没有差异。总之，巨噬细胞 LpL 在动脉粥样硬化的发展中起重要作用，但与肥胖无关。
