Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects.

OBJECTIVE: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. METHODS: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux. RESULTS: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P=0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (P<0.001), directly with arterial insulin concentration (P<0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P=0.044). CONCLUSION: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.