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

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.

Consumption of polyunsaturated fat improves the saturated fatty acid‐mediated impairment of HDL antioxidant potential

“…In contrast with the critical role of cholesterol on macrophage‐to‐feces RCT , the amount of dietary PUFA did not affect the rate of fecal macrophage‐derived [ 3 H]cholesterol excretion, despite affecting HDL lipid composition. While these results contrast with the enhancing effects of n‐3 fatty acids C20:5 EPA and C22:6 DHA on macrophage‐to‐feces RCT in mice and hamsters , they are consistent with the reported absence of effects when low‐ and high‐soybean oil‐enriched diets were compared in mice . As with the HFHC‐SFA diet , HFHC enriched with C20:5 DHA and C22:6 EPA also upregulated Abcg5 and Abcg8 and accelerated the rate of fecal excretion of HDL‐derived cholesterol .…”

Conjugated Linoleic Acid and Alpha Linolenic Acid Improve Cholesterol Homeostasis in Obesity by Modulating Distinct Hepatic Protein Pathways

“…Importantly, cholesterol content within the diets was equivalent across all groups and thus results observed are independent of dietary cholesterol levels. In contrast to previous studies with EPA/DHA we did not demonstrate an increase in ABCG5/8 expression or fecal 3 H‐cholesterol elimination after ALA‐HFD or CLA‐HFD relative to LFD. Differences in animal models, dosing, duration of supplementation, and dietary fatty acid composition may account for these differences between studies.…”

“…Previous studies have shown that enrichment of HFDs with the PUFAs EPA and DHA enhance macrophage‐to‐feces RCT . Kasbi Chadli et al.…”

“…Kasbi Chadli et al. demonstrated that an EPA/DHA enriched HFD (4.5% kcal from n‐3 PUFA) increased fecal bile acid and cholesterol excretion in hamsters coincident with increased ABCG5 and SR‐BI mRNA expression relative to both chow and HFD groups . Nishimoto et al.…”

“…Hepatic expression of ABCG5/8 and ABCB11, which shuttle free cholesterol and bile acids to the gall bladder, respectively, were significantly downregulated after SFA‐HFD relative to low‐fat diet (LFD) control. HFDs enriched with omega‐3 (n‐3) fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), have been shown to enhance macrophage‐to‐feces RCT coincident with increased expression of ABCG5/8 . Similarly enrichment of a HFD with cholesterol significantly increased macrophage‐to‐faeces RCT due to upregulation in ABCG5/8 expression .…”