Abstract
Lecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism. We evaluated the influence of insulin sensitivity and of the TaqIB CETP gene polymorphism (B1B2) on plasma LCAT, CETP, and PLTP activities (measured with exogenous substrates) and their responses to hyperinsulinemia. Thirty-two non-diabetic men without hyperlipidemia were divided in quartiles of high (Q1) to low (Q4) insulin sensitivity. Plasma total cholesterol, very low + low density lipoprotein cholesterol, triglycerides, and apolipoprotein (apo) B were higher in Q4 compared to Q1 (P < 0.05 for all), whereas HDL cholesterol and apoA-I were lowest in Q4 (P < 0.05 for both). Plasma LCAT activity was higher in Q4 than in Q1 (P < 0.05) and PLTP activity was higher in Q4 than in Q2 (P < 0.05). Insulin sensitivity did not influence plasma CETP activity. Postheparin plasma lipoprotein lipase activity was highest and hepatic lipase activity was lowest in Q1. Insulin infusion decreased PLTP activity (P < 0.05), irrespective of the degree of insulin sensitivity. The CETP genotype exerted no consistent effects on baseline plasma lipoproteins and LCAT, CETP, and PLTP activities. The decrease in plasma PLTP activity after insulin was larger in B1B1 than in B2B2 homozygotes (P < 0.05).▪These data suggest that insulin sensitivity influences plasma LCAT, PLTP, lipoprotein lipase, and hepatic lipase activities in men. As PLTP, LCAT, and hepatic lipase may enhance reverse cholesterol transport, it is tempting to speculate that high levels of these factors in association with insulin resistance could be involved in an antiatherogenic mechanism. A possible relationship between the CETP genotype and PLTP lowering by insulin warrants further study.—Riemens, S. C., A. Van Tol, B. K. Stulp, and R. P. F. Dullaart. Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men. J. Lipid Res. 1999. 40: 1467–1474.
Highlights
Lecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism
HDL metabolism is governed by lipoprotein lipase (LPL) and hepatic lipase (HL) in such a way that LPL-mediated hydrolysis of triglyceride-rich lipoproteins enhances the incorporation of lipoprotein surface constituents in HDL [10, 12] and that HL stimulates HDL triglyceride hydrolysis [12] and pre-HDL generation [13]
This study suggests that insulin sensitivity influences LPL and HL activities in postheparin plasma, as well as plasma LCAT and PLTP, but not CETP activity in nondiabetic men
Summary
The study was approved by the local medical ethics committee and all participants provided written informed consent. The participants did not change their dietary habits at least 2 weeks prior to the study and they did not consume alcohol on the day before the study. They were fasting from 20.00 h onwards. One hand vein was cannulated and the intravenous catheter was kept patent with a NaCl drip (154 mmol/l, 30 ml/h) This hand was placed in a thermoregulated box with an ambient temperature of 55ЊC in order to obtain arterialized venous blood. Blood glucose was measured at 5–10-min intervals and its target level during the clamp was approximately 0.4 mmol/l below the fasting level. The mean glucose infusion rate (M value in mol/kg/ min) during the third hour of the clamp was calculated as a measure of insulin sensitivity.
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