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A more recent version of this article appeared on August 1, 2003

Papers In Press, published online ahead of print May 16, 2003
J. Lipid Res., doi:10.1194/jlr.M300008-JLR200
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Submitted on January 7, 2003
Revised on May 2, 2003
Accepted on May 2, 2003

Decreased PLTP mass but elevated PLTP activity, linked to insulin resistance, in hypertriglyceridemia: effects of bezafibrate therapy

Iris J.A.M. Jonkers, Augustinus H.M. Smelt, Hiroaki Hattori, Leo M. Scheek, Teus van Gent, Frits H.A.F. de Man, Arnoud van der Laarse, and Arie van Tol

General Internal Medicine, Leiden University Medical Center, Leiden 2300 RC

Corresponding Author: a.h.m.smelt{at}lumc.nl

Hypertriglyceridemia (HTG) is associated with insulin resistance, increased cholesteryl ester transfer (CET) and low HDL-cholesterol (HDL-C). Phospholipid transfer protein (PLTP) may be involved in these relationships. Associations between CET, lipids, insulin resistance, CETP- and PLTP activities and PLTP mass were investigated in 18 HTG patients and 20 controls. The effects of 6-weeks bezafibrate treatment on these parameters were studied in a randomized controlled trial in HTG patients. HTG patients had significantly higher serum triglycerides, insulin resistance, FFA and CET, lower levels of HDL-C (-44%) and PLTP mass (-54%), and higher CETP (+20%) and PLTP activities (+48%), compared to controls. Bezafibrate significantly reduced serum triglycerides, CET (-37%), insulin resistance (-53%), FFA (-48%), CETP activity (-12%), PLTP activity (-8%) and increased HDL-C (+27%), whereas PLTP mass remained unchanged. Regression analysis showed a significant positive contribution of PLTP mass (p=0.001) but not of PLTP activity to HDL-C, whereas insulin resistance positively contributed to PLTP activity levels (p<0.01). Bezafibrate-induced change in CET and HDL-C levels correlated significantly with changes in CETP activity and FFA levels, but not with a change in PLTP activity. Bezafibrate-induced change in PLTP activity correlated with change in FFA levels (r=0.455, p=0.058). We propose that the elevated PLTP activity in HTG is related to insulin resistance and not to increased PLTP mass. Bezafibrate-induced diminished insulin resistance is associated with a reduction of both CET and PLTP activity.


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