Adipose tissue-specific CETP expression in mice: impact on plasma lipoprotein metabolism.
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.
Zhou
Hongwen
H
Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
Li
Zhiqiang
Z
Hojjati
Mohamad R
MR
Jang
David
D
Beyer
Thomas P
TP
Cao
Guoqing
G
Tall
Alan R
AR
Jiang
Xian-Cheng
XC
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000032:analysis / Q000097:blood; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics
D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D002787:Sterol Esterase