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Journal of Lipid Research, Vol. 44, 1462-1469, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Decreased PLTP mass but elevated PLTP activity linked to insulin resistance in HTG

Iris J. A. M. Jonkers^*, Augustinus H. M. Smelt^1,*, Hiroaki Hattori, Leo M. Scheek^**, Teus van Gent^**, Frits H. A. F. de Man, Arnoud van der Laarse and Arie van Tol^**

^* Departments of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Research Division, R&D Center, BML, Inc., 1361-1 Matoba, Kawagoe, Saitama, Japan
^** Department of Biochemistry, Erasmus Medical Center, Rotterdam, The Netherlands

¹ To whom correspondence should be addressed. e-mail: a.h.m.smelt{at}lumc.nl

Hypertriglyceridemia (HTG) is associated with insulin resistance, increased cholesteryl ester transfer (CET), and low HDL cholesterol. 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. Effects of 6 weeks of bezafibrate treatment were studied in HTG patients. HTG patients had higher serum triglycerides, insulin resistance, free fatty acid (FFA), and CET, lower levels of HDL cholesterol (-44%) and PLTP mass (-54%), and higher CETP (+20%) and PLTP activity (+48%) than controls. Bezafibrate reduced triglycerides, CET (-37%), insulin resistance (-53%), FFA (-48%), CETP activity (-12%), PLTP activity (-8%), and increased HDL cholesterol (+27%), whereas PLTP mass remained unchanged. Regression analysis showed a positive contribution of PLTP mass (P = 0.001) but not of PLTP activity to HDL cholesterol, whereas insulin resistance positively contributed to PLTP activity (P < 0.01). Bezafibrate-induced change in CET and HDL cholesterol correlated with changes in CETP activity and FFAs, but not with change in PLTP activity. Bezafibrate-induced change in PLTP activity correlated with change in FFAs (r = 0.455, P = 0.058). We propose that 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 CET and PLTP activity.

Abbreviations: CET, cholesteryl ester transfer; CETP, cholesteryl ester transfer protein; CVD, cardiovascular disease; FFA, free fatty acid; HTG, hypertriglyceridemia; PLTP, phospholipid transfer protein; PPAR, peroxisome proliferator-activated receptor

Supplementary key words phospholipid transfer protein • cholesteryl ester transfer • triglycerides • hypertriglyceridemia

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