Abstract 173: Sodium Salicylate Modulates Reverse Cholesterol Transport and HDL Proteome within Obesity

Abstract

Obesity is associated with increased risk of cardiovascular disease (CVD) due to imbalances in lipid metabolism and leads to maladaptive inflammatory responses. This study assessed the effects of an obesogenic diet supplemented with anti-inflammatory sodium salicylate (NaS) on hepatic health, HDL proteomic quality, HDL functionality and Reverse Cholesterol Transport (RCT). RCT was assessed after 24 weeks in C57BL/6 mice fed a high fat (HFD) (60% fat) ± NaS (6g/kg) diet or low-fat diet (LFD, 10% fat) by tracing 3 H-cholesterol movement from labelled macrophages, injected intraperitoneally, into plasma, liver and fecal compartments. HDL particles were separated from plasma by fast protein liquid chromatography (FPLC) and associated proteins were identified by mass spectrometry. HDL particles were incubated with 3 H-cholesterol-labelled macrophages ex vivo and cholesterol efflux to HDL particles was determined by liquid scintillation counting (LSC). Both HFDs significantly increased HDL cholesterol mass. Nonetheless, HFD alone impaired hepatic movement of 3 H-cholesterol to fecal compartments coincident with increased hepatic lipid infiltration and inflammation. NaS supplementation increased all steps of macrophage-to-feces RCT with partial preservation of hepatic transporters while impeding hepatic lipid load and reducing markers of inflammation (ALT & AST). HFD resulted in enrichment of HDL particles with coagulant proteins (fibrinogen, coagulation factor IX) and a dissociation of anti-thrombin and angiotensinogen compared to HFD+NaS. NaS supplementation also preserved ABCA1-mediated efflux capacity of HDL particles. Obesogenic diets augmented with NaS resulted in profound differences within the RCT pathway and HDL proteome. HFD supplemented with NaS was associated with improved hepatic condition and HDL proteomic profile with an increase of anticoagulant and anti-atherogenic proteins on HDL despite development of obesity.