Omega 3 Fatty Acids Promote Macrophage Reverse Cholesterol Transport in Hamster Fed High Fat Diet

Fatima Kasbi Chadli,Patrick Nguyen,Hassane Nazih,Khadija Ouguerram,Michel Krempf,Shree Ram Singh

doi:10.1371/journal.pone.0061109

Abstract

The aim of this study was to investigate macrophage reverse cholesterol transport (RCT) in hamster, a CETP-expressing species, fed omega 3 fatty acids (ω3PUFA) supplemented high fat diet (HFD). Three groups of hamsters (n = 6/group) were studied for 20 weeks: 1) control diet: Control, 2) HFD group: HF and 3) HFD group supplemented with ω3PUFA (EPA and DHA): HFω3. In vivo macrophage-to-feces RCT was assessed after an intraperitoneal injection of 3H-cholesterol-labelled hamster primary macrophages.Compared to Control, HF presented significant (p<0.05) increase in body weight, plasma TG (p<0.01) and cholesterol (p<0.001) with an increase in VLDL TG and in VLDL and LDL cholesterol (p<0.001).Compared to HF, HFω3 presented significant decrease in body weight. HFω3 showed less plasma TG (p<0.001) and cholesterol (p<0.001) related to a decrease in VLDL TG and HDL cholesterol respectively and higher LCAT activity (p<0.05) compared to HF. HFω3 showed a higher fecal bile acid excretion (p<0.05) compared to Control and HF groups and higher fecal cholesterol excretion (p<0.05) compared to HF. This increase was related to higher gene expression of ABCG5, ABCA1 and SR-B1 in HFω3 compared to Control and HF groups (<0.05) and in ABCG1 and CYP7A1 compared to HF group (p<0.05). A higher plasma efflux capacity was also measured in HFω3 using 3H- cholesterol labeled Fu5AH cells.In conclusion, EPA and DHA supplementation improved macrophage to feces reverse cholesterol transport in hamster fed HFD. This change was related to the higher cholesterol and fecal bile acids excretion and to the activation of major genes involved in RCT.

Highlights

Metabolic syndrome is a common pathological situation leading to an increase in cardiovascular disease
We investigated in hamster cholesterol ester transfer protein (CETP) species, whether omega 3 fatty acids supplemented high fat diet can modulate in vivo macrophage-to-feces reverse cholesterol transport (RCT) using hamster primary macrophages
In the present study performed in hamster, we showed that v3PUFA prevented the increase of plasma TG and cholesterol by decreasing VLDL TG and HDL cholesterol concentrations respectively

Summary

Introduction

Metabolic syndrome is a common pathological situation leading to an increase in cardiovascular disease. A low plasma HDL-cholesterol concentration does not always predict an increase of the cardiovascular risk and deeper understanding of HDL metabolism could help to define the critical situations. The cholesterol ester transfer protein (CETP) plays a critical role in RCT and performs, in parallel to direct uptake of HDL cholesterol by liver, transfer of cholesterol from HDL to LDL followed by liver LDL uptake. This metabolism is very complex and to study its modulation, it is easier to use animal models. CETP pathway would represent a major route for human RCT [7] and CETP expressing species, as hamster, represents a better model to investigate lipoprotein metabolism [8]

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