Biochem. J. (2009) 419
(629–634) (Printed in Great Britain)
Cholesteryl ester transfer protein (CETP) increases postprandial triglyceridaemia and delays triacylglycerol plasma clearance in transgenic mice
Alessandro G. SALERNO, Patrícia R. PATRÍCIO, Jairo A. BERTI and Helena C. F. OLIVEIRA1
Departamento Fisiologia e Biofísica, Instituto de Biologia, UNICAMP (Universidade Estadual de Campinas), Campinas 13083-862, SP, Brazil
The CETP (cholesteryl ester transfer protein) is a plasma protein synthesized in several tissues, mainly in the liver; CETP reduces plasma HDL (high-density lipoprotein) cholesterol and increases the risk of atherosclerosis. The effect of CETP levels on postprandial intravascular metabolism of TAGs (triacylglycerols) is an often-overlooked aspect of the relationship between CETP and lipoprotein metabolism. Here, we tested the hypothesis that CETP delays the plasma clearance of TAG-rich lipoprotein by comparing human CETP expressing Tg (transgenic) and non-Tg mice. After an oral fat load, the postprandial triglyceridaemia curve was markedly increased in CETP-Tg compared with non-Tg mice (280±30 versus 190±20 mg/dl per 6 h respectively, P<0.02). No differences in intestinal fat absorption and VLDL (very-low-density lipoprotein) secretion rates were observed. Kinetic studies of double-labelled chylomicron-like EMs (emulsions) showed that both [3H]triolein and [14C]cholesteryl oleate FCRs (fractional clearance rates) were significantly reduced (∼20%) in CETP-Tg mice. Furthermore, TAG from lipid EM pre-incubated with CETP-Tg plasma had plasma clearance and liver uptake significantly lower than the non-Tg plasma-treated lipid EM. In addition, reductions in post-heparin plasma LPL (lipoprotein lipase) activity (50%) and adipose tissue mRNA abundance (39%) were verified in CETP-Tg mice. Therefore we conclude that CETP expression in Tg mice delays plasma clearance and liver uptake of TAG-rich lipoproteins by two mechanisms: (i) transferring TAG to HDLs and increasing CE content of the remnant particles and (ii) by diminishing LPL expression. These findings show that the level of CETP expression can influence the responsiveness to dietary fat and may lead to fat intolerance.
Key words: cholesteryl ester transfer protein (CETP), fat tolerance, lipoprotein lipase, postprandial lipoprotein, remnant, transgenic mice.
Abbreviations used: CE, cholesteryl ester; CETP, CE transfer protein; EM, emulsion; NEFA, non-esterified fatty acid; FCR, fractional clearance rate; HDL, high-density lipoprotein; HL, hepatic lipase; LDL, low-density lipoprotein; LPL, lipoprotein lipase; LRP, LDL receptor related protein; Tg, transgenic; TAG, triacylglycerol; VLDL, very-low-density lipoprotein.
1To whom correspondence should be addressed (email ho98@unicamp.br).
Received 25 June 2008/22 January 2009; accepted 4 February 2009
Published as BJ Immediate Publication 4 February 2009, doi:10.1042/BJ20081299
© The Authors Journal compilation © 2009 Biochemical Society
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