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.
Highlights
Adipose tissue appears to be a highly conserved site of cholesteryl ester transfer protein (CETP) expression across species
CETP mRNA was predominantly expressed in adipose tissue in lines 1-3 and 1-9 (Fig. 2A)
We found that peroxisome proliferator-activated receptor g (PPARg), SREBP1c, and LPL mRNA levels were significantly decreased in aP2-CETP transgenic (CETPTg) mice compared with WT mice (Fig. 7A–C), whereas hormone-sensitive lipase (HSL) mRNA levels did not change (Fig. 7D)
Summary
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 tissuespecific CETP transgenic (CETPTg) mice. In addition to studies of physiological regulation, the release of CETP activity from cultured hamster adipose tissue increased after a period of fasting [16]. Despite these correlative findings, there is no direct evidence that adipose-derived CETP enters the circulation or that it influences plasma lipoprotein levels. There is no direct evidence that adipose-derived CETP enters the circulation or that it influences plasma lipoprotein levels To investigate these issues, we established adipose tissue-specific CETPTg mouse lines
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