Zhou Hongwen, Li Zhiqiang, Hojjati Mohamad R, Jang David, Beyer Thomas P, Cao Guoqing, Tall Alan R, Jiang Xian-Cheng
Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
J Lipid Res. 2006 Sep;47(9):2011-9. doi: 10.1194/jlr.M600153-JLR200. Epub 2006 Jun 2.
Adipose tissue appears to be a highly conserved site of cholesteryl ester transfer protein (CETP) expression across species. To investigate the impact of adipose CETP expression on lipid metabolism, we created adipose tissue-specific CETP transgenic (CETPTg) mice. CETP mRNA is predominantly expressed in adipose tissue. Plasma CETP mass and activity are readily detectable in CETPTg mice but not in controls. Plasma lipoprotein analysis shows marked reductions in HDL cholesterol and phospholipids, increases non-HDL lipids, decreases apolipoprotein A-I (apoA-I), and increases apoB. Unexpectedly, CETPTg adipocytes are significantly smaller than those in control mice (44%), triglyceride and cholesterol in adipose tissue were significantly decreased compared with controls (50% and 37%, respectively), and phospholipids showed no significant changes. To study the mechanism, we measured peroxisome proliferator-activated receptor gamma, sterol-regulatory element binding protein-1c, LPL, and hormone-sensitive lipase (HSL) in aP2-CETPTg adipose tissue and controls and found that, except for HSL, all mRNA levels are significantly decreased in the transgenic mice compared with controls (26, 33, and 22%). In conclusion, adipose tissue CETP makes a major contribution to CETP in the circulation, reduces HDL, and increases non-HDL cholesterol levels. Moreover, adipose tissue CETP expression changes triglyceride and cholesterol content and the size of adipocytes.
脂肪组织似乎是跨物种中胆固醇酯转运蛋白（CETP）表达高度保守的位点。为了研究脂肪组织中CETP表达对脂质代谢的影响，我们构建了脂肪组织特异性CETP转基因（CETPTg）小鼠。CETP mRNA主要在脂肪组织中表达。在CETPTg小鼠中可轻易检测到血浆CETP质量和活性，而在对照小鼠中则检测不到。血浆脂蛋白分析显示高密度脂蛋白胆固醇和磷脂显著降低，非高密度脂蛋白脂质增加，载脂蛋白A-I（apoA-I）降低，载脂蛋白B增加。出乎意料的是，CETPTg脂肪细胞明显小于对照小鼠中的脂肪细胞（小44%），脂肪组织中的甘油三酯和胆固醇与对照相比显著降低（分别降低50%和37%），而磷脂无显著变化。为了研究其机制，我们测量了aP2-CETPTg脂肪组织和对照中的过氧化物酶体增殖物激活受体γ、固醇调节元件结合蛋白-1c、脂蛋白脂肪酶（LPL）和激素敏感性脂肪酶（HSL），发现与对照相比，除HSL外，转基因小鼠中所有mRNA水平均显著降低（分别降低26%、33%和22%）。总之，脂肪组织中的CETP对循环中的CETP有主要贡献，降低高密度脂蛋白，并增加非高密度脂蛋白胆固醇水平。此外，脂肪组织中CETP的表达改变甘油三酯和胆固醇含量以及脂肪细胞大小。
