Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
J Lipid Res. 2010 Jan;51(1):97-102. doi: 10.1194/jlr.M900186-JLR200.
The cholesteryl ester transfer protein (CETP) facilitates the bidirectional transfer of cholesteryl esters and triglycerides (TG) between HDL and (V)LDL. By shifting cholesterol in plasma from HDL to (V)LDL in exchange for VLDL-TG, CETP aggravates atherosclerosis in hyperlipidemic APOE*3-Leiden (E3L) mice. The aim of this study was to investigate the role of CETP in TG metabolism and high-fat diet-induced obesity by using E3L mice with and without the expression of the human CETP gene. On chow, plasma lipid levels were comparable between both male and female E3L and E3L.CETP mice. Further mechanistic studies were performed using male mice. CETP expression increased the level of TG in HDL. CETP did not affect the postprandial plasma TG response or the hepatic VLDL-TG and VLDL-apolipoprotein B production rate. Moreover, CETP did not affect the plasma TG clearance rate or organ-specific TG uptake after infusion of VLDL-like emulsion particles. In line with the absence of an effect of CETP on tissue-specific TG uptake, CETP also did not affect weight gain in response to a high-fat diet. In conclusion, the CETP-induced increase of TG in the HDL fraction of E3L mice is not associated with changes in the production of TG or with tissue-specific clearance of TG from the plasma.
胆固醇酯转移蛋白（CETP）促进胆固醇酯和甘油三酯（TG）在高密度脂蛋白（HDL）和极低密度脂蛋白（VLDL）之间的双向转移。通过将血浆中的胆固醇从 HDL 转移到 VLDL 以换取 VLDL-TG，CETP 加剧了高脂血症 APOE*3-Leiden（E3L）小鼠的动脉粥样硬化。本研究的目的是通过表达人 CETP 基因的 E3L 小鼠和不表达人 CETP 基因的 E3L 小鼠来研究 CETP 在 TG 代谢和高脂肪饮食诱导肥胖中的作用。在正常饮食下，雄性和雌性 E3L 和 E3L.CETP 小鼠的血浆脂质水平相当。进一步的机制研究使用雄性小鼠进行。CETP 表达增加了 HDL 中的 TG 水平。CETP 不影响餐后血浆 TG 反应或肝 VLDL-TG 和 VLDL-载脂蛋白 B 生成率。此外，CETP 不影响输注 VLDL 样乳液颗粒后血浆 TG 清除率或器官特异性 TG 摄取。与 CETP 对组织特异性 TG 摄取没有影响一致，CETP 也不影响高脂肪饮食引起的体重增加。总之，E3L 小鼠中 CETP 诱导的 HDL 中 TG 增加与 TG 产生或从血浆中清除组织特异性 TG 的变化无关。
