Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism.

J Lipid Res 2012 Jun 2;53(6):1190-9. Epub 2012 Apr 2.

Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.

Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A subset of the subjects not treated with atorvastatin participated in a third phase (n = 6), in which they received torcetrapib 120 mg twice daily for an additional 4 weeks. At the end of each phase, all subjects received a primed-constant infusion of [5,5,5-(2)H(3)]L-leucine, while in the constantly fed state, to determine the kinetics of TRL apoB-48 and TRL composition. Relative to placebo, torcetrapib markedly reduced TRL CE levels in all groups (≥-69%; P < 0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the nonatorvastatin once daily (PS: -49%, P = 0.007; PR: -49%, P = 0.005) and twice daily (PS: -30%, P = 0.01; PR: -27%, P = 0.13) cohorts. In the atorvastatin cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not change with torcetrapib. Our findings indicate that CETP inhibition reduced plasma apoB-48 concentrations by reducing apoB-48 production but did not have this effect in subjects already treated with atorvastatin.

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http://www.jlr.org/lookup/doi/10.1194/jlr.M019570
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http://dx.doi.org/10.1194/jlr.M019570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351826PMC
June 2012
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References

(Supplied by CrossRef)
Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich-remnant lipoproteins
Zilversmit et al.
Clin. Chem. 1995

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