Mechanisms
Adipose-specific CETP expression alone lowers HDL cholesterol and shrinks adipocytes in mice (J Lipid Res 2006)
Original title: Adipose tissue-specific CETP expression in mice: impact on plasma lipoprotein metabolism
In mice engineered to express human CETP specifically in adipose tissue, plasma CETP mass and activity were readily detectable versus undetectable in controls. These mice showed marked reductions in HDL cholesterol and phospholipids, increased non-HDL lipids, decreased apoA-I, and increased apoB. Unexpectedly, CETP-transgenic adipocytes were 44% smaller than controls, with adipose triglyceride and cholesterol reduced 50% and 37% respectively, while phospholipids were unchanged. Adipose PPARgamma, SREBP-1c, and LPL mRNA were each significantly decreased (26%, 33%, and 22% respectively) in transgenic tissue, while hormone-sensitive lipase was unaffected, indicating adipose tissue alone is a major contributor to circulating CETP and that its local expression reshapes both systemic lipoproteins and adipocyte lipid content and size.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.