Abstract 1084: Effect of Weight Loss on Macrophage Cholesterol Efflux to Plasma of Obese Individuals With Metabolic Syndrome
Background: Metabolic syndrome (MetS) includes hypertriglyceridemia (HTG) and low HDL-cholesterol. Macrophage cholesterol efflux (MCE) to HDL initiates reverse cholesterol transport (RCT). MCE to HTG plasma is higher than that to normolipidemic (NL) plasma. However, the effect of reducing HTG with weight loss on MCE in MetS is unknown.
Method: The human THP1 macrophage cell line was labeled with [3H]cholesterol, activated with LXR agonist to upregulate ABCA1 and exposed to diluted plasma (3%) from MetS patients (n=22, BMI=41.7) before and after 6 weeks of very low calorie diet-induced weight loss and from NL controls (n=20, BMI=23). MCE was expressed as percent cellular [3H]cholesterol efflux to plasma. Size exclusion chromatography (SEC) identified lipoproteins accumulating [3H]cholesterol in two samples for qualitative comparison.
Results: Mean weight loss among MetS patients was 18.6 lbs. MetS baseline MCE was higher than that of controls (p=0.006), decreased by 18% after weight loss (p=0.006) and correlated with plasma triglyceride (p=0.036, r=0.482). MCE correlated with plasma apoB in controls (p=<0.001, r=0.883) and MetS post weight loss, mean TG reduction 52 mg/dL (p=0.012, r=0.767). SEC revealed greater fraction of cellular cholesterol accumulated in VLDL and LDL in MetS baseline versus control.
Conclusion: HTG in MetS enhances MCE. Weight loss in MetS reduces MCE to levels comparable to that of control values. In NL, apoB correlates directly with efflux implying that apoB-containing lipoproteins drive MCE. We conclude that decreased macrophage cholesterol efflux with weight loss is due to the concurrent reduction in the number of lipoprotein acceptors.