Lyso‐diacylglyceryltrimethylhomoserine (lyso‐DGTS) isolated from Nannochloropsis microalgae improves high‐density lipoprotein (HDL) functions

Abstract

Many population studies have shown that blood concentrations of high-density lipoprotein (HDL) cholesterol are inversely correlated with risk of cardiovascular disease (CVD). However, in recent studies, increasing blood HDL cholesterol concentrations failed to reduce CVD events. On the other hand, studies suggest that improving HDL quality can be a more efficient tool for assessing atherosclerotic risk than simply measuring blood HDL cholesterol concentration. Thus, improving HDL activity using natural substances might be a useful therapeutic approach to reducing CVD risk. We previously isolated a novel active compound from Nannochloropsis microalgae termed lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS), which increased activity of paraoxonase 1, the main antioxidant enzyme associated with HDL. Here we examined the effect of lyso-DGTS on HDL quality and function. Tryptophan-fluorescence-quenching assay showed that lyso-DGTS interacts spontaneously with the entire HDL lipoprotein and with apolipoprotein A1 (ApoA1), the major structural and functional HDL protein, with high affinity (K a = 2.17 × 10 4 M −1 at 37 C). Lyso-DGTS added to HDL and to ApoA1 increased cholesterol efflux from macrophage cells, the main antiatherogenic function of HDL, dose-dependently, and significantly increased HDL's ability to induce nitric oxide production from endothelial cells. In-vivo supplementation of lyso-DGTS to the circulation of mice fed a high-fat diet via osmotic mini-pumps implanted subcutaneously enhanced HDL anti-inflammatory effect significantly as compared to controls. Our findings suggest that lyso-DGTS may have a beneficial effect in decreasing atherosclerosis risk by interacting with HDL particles and improving their quality and antiatherogenic functions.

Effects of Structural and Compositional Changes of Nanochloropsis oceania after Enzyme Treatment on EPA-Rich Lipids Extraction

“…Here, we observed a significant increase in betaine-lipid LDGTS content, consistent with a prior Nannochloropsis study, in which ethanol-based lipid extraction achieved the highest LDGTS content [ 36 ]. LDGTS extracts can increase paraoxonase 1 (PON1) activity, thereby protecting macrophages and low-density lipoprotein, and possibly improving high-density lipoprotein and anti-atherogenic function [ 37 ]. In summary, our combined enzyme treatment with ethanol effectively extracted LDGTS from Nannochloropsis lipids.…”

Lyso-DGTS Lipid Derivatives Enhance PON1 Activities and Prevent Oxidation of LDL: A Structure–Activity Relationship Study

“…The synthesized and purchased lyso-DGTS derivatives and analogs (final concentration 10 and 20 µg/mL) were incubated with rePON1 for 2 and 4 h at 37 °C in Tris buffer pH 8.4 containing 1 mM CaCl 2 . These concentrations were chosen in accordance with our previous published studies which showed that, in these concentrations, lyso-DGTS has a positive effect on PON1 and HDL activities in vitro and in vivo without inducing a cytotoxic response [ 23 , 24 , 25 ].…”

“…The assay was performed as previously published in our studies [ 25 , 26 ]. Briefly, in 200 μL Tris buffer in a black 96-well plate, 2 μL of bioactive lipid (in DMSO) at various final concentrations (1, 5, 10, 25, 50, 75, and 100 μg/mL) and rePON1 (final concentration 50 µg/mL) were incubated at 37 °C or 25 °C for 4 h; then, fluorescence measurements were performed in a plate reader (Tecan Infinite 200 PRO).…”

“…In our previous studies, lyso-DGTS was found to protect macrophages and LDL from oxidation and potentially improve HDL function by increasing the activity of PON1 [ 24 ]. Moreover, we showed that lyso-DGTS lipid interacts with HDL proteins and with the HDL core, improving HDL functions in vitro and in vivo [ 25 ].…”

S-Nitrosylation of Paraxonase 1 (PON1) Elevates Its Hydrolytic and Antioxidant Activities

“…High-density lipoprotein (HDL) particles play a major role in preventing atherosclerosis development because of their anti-atherosclerotic properties-collecting excess cholesterol and returning it to the liver, exhibiting antioxidant and anti-inflammatory properties, and improving endothelial cell function [6,10,11]. Paraoxonase 1 (PON1) is a glycoprotein enzyme that is synthesized in the liver and transferred to the bloodstream, where it binds to the HDL particles and confers many of their anti-atherosclerotic properties [12,13].…”