出版社:American Society for Biochemistry and Molecular Biology
摘要:Adipose tissue appears to be a highly conserved site of cholesterylester transfer protein (CETP) expression across species. Toinvestigate 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 CETPTgmice but not in controls. Plasma lipoprotein analysis showsmarked reductions in HDL cholesterol and phospholipids, increasesnon-HDL lipids, decreases apolipoprotein A-I (apoA-I), and increasesapoB. Unexpectedly, CETPTg adipocytes are significantly smallerthan those in control mice (44%), triglyceride and cholesterolin adipose tissue were significantly decreased compared withcontrols (50% and 37%, respectively), and phospholipids showedno significant changes. To study the mechanism, we measuredperoxisome proliferator-activated receptor , sterol-regulatoryelement 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 decreasedin the transgenic mice compared with controls (26, 33, and 22%).In conclusion, adipose tissue CETP makes a major contributionto CETP in the circulation, reduces HDL, and increases non-HDLcholesterol levels. Moreover, adipose tissue CETP expressionchanges triglyceride and cholesterol content and the size ofadipocytes.Supplementary key words cholesteryl ester transfer protein • adipocyte • transgenic mice