Abstract P220: The Effect of Diet-Induced Weight Loss on HDL Functionality in Individuals with Metabolic Syndrome: Investigating Alteration of the Initial Step in Reverse Cholesterol Transport as a Function of Plasma Lipoprotein Composition
The prevalence of metabolic syndrome (MetS) with obesity-linked diabetes continues to increase globally and is associated with atherogenic dyslipidemia characterized by high triglycerides (TG), small, dense low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C) levels. HDL orchestrates the reverse cholesterol transport (RCT) process, initiated by macrophage cholesterol efflux (MCE). The traditional hypothesis is that individuals with dyslipidemia have impaired RCT that leads to atherogenesis. However, a recent study showed that one metric of HDL function, macrophage cholesterol efflux (MCE) to diluted patient plasma, inversely correlated with atherosclerotic burden, independent of plasma HDL-C levels. Moreover, cholesterol efflux from ABCA1-upregulated macrophage cell lines to sera of diabetic hypertriglyceridemic subjects is enhanced compared to normolipidemic (NL) controls. The effect of weight loss on MCE in obese individuals with MetS is unknown. The purpose of this study is to evaluate MCE in obese individuals with MetS as a function of plasma dyslipidemia, and to determine the effect of weight loss on the RCT process. We measured the rate of MCE from human monocytic leukemia THP1 cells to plasma of NL controls (n=24) and obese MetS (n=24) patients before and after 4 to 6 weeks of very low calorie, diet-induced weight loss. Weight loss in the MetS patients was significant, averaged 21.3 lbs, with concurrent significant decreases in TG, apoB, TC, LDL-C and non-HDL-C. Measures of insulin resistance, systolic blood pressure and kidney function improved with weight loss. HDL-C was not significantly altered, but apoA-I decreased with weight loss. MCE to plasma of obese MetS patients was higher than MCE to control plasma ((7.44 + 1.36) % vs (6.39 + 1.23) %, p=0.0069). MCE to plasma of obese MetS patients significantly decreased after weight loss (6.23 + 1.69) %, comparable to control values. MCE was strongly correlated to apoB levels (r2 = 0.13 - 0.38), consistent with apoB lipoprotein function as a cholesterol sink. This was confirmed by size exclusion chromatography analysis of the distribution of effluxed cholesterol among plasma lipoproteins in 1 control and 2 Mets patients. In conclusion, obese patients with MetS demonstrate increased MCE, a measure of HDL function, compared to NL controls, which significantly decreases in response to diet-induced weight loss, concurrent with a reduction in triglyceride and apoB levels. These results suggest that the high apoB lipoprotein levels in MetS pateints facilitate MCE, and may at least partially compensate for the low HDL-C to promote RCT in these patients.
- © 2012 by American Heart Association, Inc.