CETP does not affect triglyceride production or clearance in APOE*3-Leiden mice.
The cholesteryl ester transfer protein (CETP) facilitates the bidirectional transfer of cholesteryl esters and triglycerides (TG) between HDL and (V)LDL. By shifting cholesterol in plasma from HDL to (V)LDL in exchange for VLDL-TG, CETP aggravates atherosclerosis in hyperlipidemic APOE*3-Leiden (E3L) mice. The aim of this study was to investigate the role of CETP in TG metabolism and high-fat diet-induced obesity by using E3L mice with and without the expression of the human CETP gene. On chow, plasma lipid levels were comparable between both male and female E3L and E3L.CETP mice. Further mechanistic studies were performed using male mice. CETP expression increased the level of TG in HDL. CETP did not affect the postprandial plasma TG response or the hepatic VLDL-TG and VLDL-apolipoprotein B production rate. Moreover, CETP did not affect the plasma TG clearance rate or organ-specific TG uptake after infusion of VLDL-like emulsion particles. In line with the absence of an effect of CETP on tissue-specific TG uptake, CETP also did not affect weight gain in response to a high-fat diet. In conclusion, the CETP-induced increase of TG in the HDL fraction of E3L mice is not associated with changes in the production of TG or with tissue-specific clearance of TG from the plasma.
Bijland
Silvia
S
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
van den Berg
Sjoerd A A
SA
Voshol
Peter J
PJ
van den Hoek
Anita M
AM
Princen
Hans M G
HM
Havekes
Louis M
LM
Rensen
Patrick C N
PC
Willems van Dijk
Ko
K
D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D014280:Triglycerides / Q000096:biosynthesis* / Q000097:blood
D053318:Apolipoprotein E3; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D004041:Dietary Fats; D014280:Triglycerides; C052720:apolipoprotein E3 (Leidein)