Abstract
Previous studies demonstrated that pomegranate, which is a source of several bioactive molecules, induces modifications of high-density lipoproteins (HDL) lipid composition and functionality. However, it remains unclear whether the beneficial effects of pomegranate are related to improvement in the lipid components of HDL. Therefore, in this placebo-controlled study, we characterized the size and lipid composition of HDL subclasses and assessed the functionality of these lipoproteins after 30 days of supplementation with a pomegranate microencapsulated (MiPo) in New Zealand white rabbits. We observed a significant decrease in plasma cholesterol, triglycerides, and non−HDL sphingomyelin, as well as increases in HDL cholesterol and HDL phospholipids after supplementation with MiPo. Concomitantly, the triglycerides of the five HDL subclasses isolated by electrophoresis significantly decreased, whereas phospholipids, cholesterol, and sphingomyelin of HDL subclasses, as well as the HDL size distribution remained unchanged. Of particular interest, the triglycerides content of HDL, estimated by the triglycerides-to-phospholipids ratio, decreased significantly after MiPo supplementation. The modification on the lipid content after the supplementation was associated with an increased resistance of HDL to oxidation as determined by the conjugated dienes formation catalyzed by Cu2+. Accordingly, paraoxonase-1 (PON1) activity determined with phenylacetate as substrate increased after MiPo. The effect of HDL on endothelial function was analyzed by the response to increasing doses of acetylcholine of aorta rings co-incubated with the lipoproteins in an isolated organ bath. The HDL from rabbits that received placebo partially inhibited the endothelium-dependent vasodilation. In contrast, the negative effect of HDL on endothelial function was reverted by MiPo supplementation. These results show that the beneficial effects of pomegranate are mediated at least in part by improving the functionality of HDL, probably via the reduction of the content of triglycerides in these lipoproteins.
Highlights
The inverse correlation between high-density lipoproteins (HDL)-cholesterol and coronary heart disease is well known and a role of these lipoproteins against atherosclerosis has been suggested [1,2,3,4].the mechanisms and components of HDL that explain the anti-atherogenic functionality of these lipoproteins remain unclear.HDLs are macromolecular complexes that include bioactive molecules within their structure, other than lipids and proteins
Supplementation with microencapsulated pomegranate (MiPo) was associated with a 26.5% reduction in HDL-triglycerides (HDL-Tg) plasma levels and increases of 15.3% and 7.3% for HDL-cholesterol (HDL-C) and HDL-phospholipids (HDL-Pho), respectively
Our results showed that the vasodilation of aorta rings incubated with HDL isolated from the plasma of rabbits that received placebo or MiPo supplementation was significantly lower compared with the vasodilation of aorta rings incubated in the absence of HDL
Summary
The inverse correlation between high-density lipoproteins (HDL)-cholesterol and coronary heart disease is well known and a role of these lipoproteins against atherosclerosis has been suggested [1,2,3,4].the mechanisms and components of HDL that explain the anti-atherogenic functionality of these lipoproteins remain unclear.HDLs are macromolecular complexes that include bioactive molecules within their structure, other than lipids and proteins. The components of HDL vary according to diverse pathophysiological conditions and result in functional differences of HDL; the amount of paraoxonase-1 (PON1), an enzyme carried in plasma by HDL that confers most of their antioxidant properties to these lipoproteins [5], and the anti-inflammatory capacity of HDL depend on HDL structure [6,7,8]. In this context, recent studies have demonstrated that HDL are internalized to the cytoplasm of cultured cells and deliver cholesterol and sphingomyelin during this process [9,10,11]. During lipid delivery to the cells, HDL may supply other molecules, including microRNAs (miRNAs) [14], acute phase proteins [15], and numerous hydrophobic compounds that may be associated with HDL structure [16]
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