Abstract 411: Obesity Alters the Expression of Very Low Density Lipoprotein Receptor (vldlr) Expression in Peripheral Blood Monocytes: Possible Links Between Vldlr Expression and Monocyte Phenotypes

Abstract

Objective: Very low density lipoprotein receptor (VLDLR) is a member of the low-density lipoprotein receptor family that binds multiple ligands including TG-rich lipoproteins. The role of VLDLR in lipid uptake had been demonstrated in cell culture and animal models, but little is known about the effects of obesity on VLDLR expression in human. Accordingly, we examined the impact of obesity on VLDLR expression in peripheral blood monocytes and explored possible links with monocyte inflammatory markers and circulating lipids. Subjects and measurements: Blood was collected from a total of 69 subjects including 23 normal-weight (body mass index: BMI < 25 kg/m 2 ) controls and 46 obese (BMI > 30 kg/m 2 ) subjects. Blood lipids, glucose and hormones were measured. Monocytes were isolated from buffy coats using Ficoll density centrifugation followed by magnetic separation of CD14-positive cells with magnetic beads. Expression of VLDLR, and pro- and ant-inflammatory markers of monocytes was examined by western blotting and quantitative qPCR. The uptake of labeled VLDL (DiI-VLDL) was also assessed in monocyte cultures. Results: Insulin, and total and VLDL triglycerides were increased in plasma of obese subjects. In addition, VLDLR protein and mRNA levels were significantly (p< 0.05) higher (~ 40%) in obese compared to lean subjects. Monocytes of obese subjects exhibited higher expression of IL-6 and TNF-α (+29 to 43%), but lower expression of IL-10 and CD163 (-30 to 47%). The levels of monocyte VLDLR was positively correlated with blood triglycerides and insulin, and negatively with adiponectin. The uptake of labeled VLDL, assessed by fluorescence microscope, was higher in monocytes of obese subjects. Conclusions: Our findings indicate that obesity upregulates the expression of VLDLR and pro-inflammatory markers in peripheral blood monocytes. The uptake VLDL was also increased in monocyte of obese subjects suggesting that obesity-induced VLDLR expression may explain the changes of VLDL uptake and monocyte phenotype.