INSERM, UMR 1087- CNRS UMR 6291, IRS - UN L'institut du thorax, Nantes, France.
PLoS One. 2013 Apr 22;8(4):e61109. doi: 10.1371/journal.pone.0061109. Print 2013.
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 (3)H-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 (3)H- 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.
本研究旨在探讨富含ω-3 多不饱和脂肪酸(ω3PUFA)的高脂肪饮食喂养的表达胆固醇转运蛋白(CETP)的仓鼠体内的巨噬细胞逆向胆固醇转运(RCT)。本研究共纳入 3 组仓鼠(每组 n = 6),分别接受 20 周的不同饮食处理:1)对照组:Control;2)高脂肪饮食组:HF;3)高脂肪饮食联合 ω3PUFA 组:HFω3。通过向仓鼠腹腔内注射(3)H-胆固醇标记的原代巨噬细胞,评估巨噬细胞向粪便中的 RCT。与对照组相比,HF 组体重、血浆三酰甘油(TG)(p<0.01)和胆固醇(p<0.001)显著增加,VLDL-TG 和 VLDL、LDL 胆固醇水平也相应增加(p<0.001)。与 HF 组相比,HFω3 组体重显著减轻。HFω3 组血浆 TG(p<0.001)和胆固醇(p<0.001)水平显著降低,与 VLDL-TG 和 HDL 胆固醇分别降低有关,LCAT 活性升高(p<0.05)。与对照组和 HF 组相比,HFω3 组粪便胆汁酸排泄量增加(p<0.05),与 HF 组相比,HFω3 组粪便胆固醇排泄量增加(p<0.05)。这种增加与 HFω3 组 ABCG5、ABCA1 和 SR-B1 基因表达水平高于对照组和 HF 组(p<0.05)以及 ABCG1 和 CYP7A1 基因表达水平高于 HF 组(p<0.05)有关。HFω3 组使用(3)H-胆固醇标记的 Fu5AH 细胞测量的血浆流出能力也更高。总之,在 HF 饮食喂养的仓鼠中,EPA 和 DHA 补充可改善巨噬细胞向粪便的逆向胆固醇转运。这种变化与胆固醇和粪便胆汁酸排泄的增加以及参与 RCT 的主要基因的激活有关。