The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review.

Alex Pizzini,Lukas Lunger,Ivan Tancevski,Guenter Weiss,Egon Demetz,Richard Hilbe,Christoph Ebenbichler

doi:10.3390/nu9101099

Alex Pizzini, Lukas Lunger + Show 5 more

Open Access

https://doi.org/10.3390/nu9101099

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Journal: Nutrients	Publication Date: Oct 6, 2017
Citations: 81	License type: CC BY 4.0

Affiliation: Innsbruck Medical University, Universität Innsbruck

Abstract

The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8. Based on current knowledge, we conclude that n-3 PUFAs may beneficially affect RCT, mainly by influencing high-density lipoprotein (HDL) remodeling and by promoting hepatobiliary sterol excretion.

Highlights

Ischemic heart disease is still the leading cause of death in Western societies [1]
This study revealed, as mentioned above, an increase in Reverse Cholesterol Transport (RCT) following n-3 PUFA treatment, probably due to increased expression of the main hepatic genes involved in RCT, including scavenger receptor class B type I (SR-BI) [29]
cholesteryl ester transfer protein (CETP) is a plasma glycoprotein secreted by the liver which enables the exchange of cholesteryl esters between high-density lipoprotein (HDL) and other lipoproteins, such as LDL, thereby promoting hepatic clearance of macrophage-derived cholesterol, via an indirect pathway by hepatic low-density lipoprotein receptors (LDLr)

Summary

Introduction

A strong inverse correlation between plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and the incidence of atherosclerotic-driven cardiovascular disease (CVD) has been shown previously [2,3,4]. This has led to the hypothesis that interventions aimed at increasing HDL-C levels might positively influence the risk of CVD [5]. This process describes the clearing pathways of peripheral, subendothelial macrophage- and fibroblast-derived cholesterol, either directly via HDL (hepatic uptake via scavenger receptor B-I, SR-BI), or indirectly by shifting cholesterol from HDL particles to apoB-containing lipoproteins for subsequent uptake into hepatocytes, via low-density lipoprotein receptors (LDLr) (Figure 1) [5,9]

Reverse

CEclass

Apolipoprotein

ATP-Binding