EFFECT OF ADIPOSITY ON PLASMA-LIPID TRANSFER PROTEIN ACTIVITIES - A POSSIBLE LINK BETWEEN INSULIN-RESISTANCE AND HIGH-DENSITY-LIPOPROTEIN METABOLISM

The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistanc e are not well understood. Lecithin: cholesterol acyltransferase (LCAT ) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of c holesteryl ester towards apolipoprotein B-containing lipoproteins. Pho spholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipopro teins, insulin and C-peptide in fasting plasma from eight healthy obes e men (body mass index >27 kg m(-2)) and 24 non-obese subjects. The ob ese men had lower levels of HDL cholesterol (P<0.05) and higher levels of plasma triglycerides (P<0.05), insulin (P<0.05) and C-peptide (P<0 .01), as compared to the quartile of subjects with the lowest body mas s index (BMI <22.4 kg m(-2)). CETP and PLTP activities were elevated i n the obese men by 35% (P<0.01) and by 15% (P<0.05), respectively. LCA T activity was comparable among the quartiles. Linear regression analy sis showed that CETP activity was positively correlated with body mass index (P<0.02), fasting blood glucose (P<0.05) and plasma C-peptide ( P<0.05). PLTP activity was positively related to body mass index (P<0. 01), waist to hip circumference ratio (P<0.001), as well as to fasting blood glucose (P<0.05) and plasma C-peptide (P<0.05). It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activi ties may provide a mechanism that contributes to alterations in HDL in insulin resistant states.