Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5 and ABCG8 transporter expressions in hamsters

Abstract

The hypolipidaemic effects of plant sterols are well established. However, mechanisms by which plant sterols lower plasma cholesterol levels, particularly at the molecular level, have not been clearly elucidated. The objective of the present study was to determine whether different plant sterol analogues reduce plasma cholesterol levels by up regulating the sterol transporters ABCG5 and ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were divided into eight groups. Groups 1 and 2 were fed a maize starch -casein -sucrose-based diet that did not contain cholesterol (control; Con) or the Con diet with the addition of 0·25 % cholesterol (Ch-Con). Groups 3 -8 were fed the Ch-Con diet supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and stanol mixture (50:50), 1·76 % plant sterol -fish oil esters, or 0·71 or 1·43 % stanol -ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up regulated the ABCG5 mRNA expression and tended (P¼ 0·083) to increase ABCG8 mRNA expression in the liver, but did not affect both genes' expression in the small intestine compared with the Con diet. Hamsters fed 0·7 % stanol esters showed lower plasma cholesterol levels (P,0·001) and also lower liver ABCG5 mRNA expression (P, 0·05) compared with the Ch-Con diet. Plant stanols, stanol esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in the liver and intestine although they reduced plasma cholesterol levels. These results suggest that plant sterols and their derivatives reduce plasma cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8 transporters. Cholesterol: Plant sterols: ABCG5: ABCG8: Hamsters It has been well documented that dietary supplementation with plant sterols and stanols reduces plasma cholesterol levels in human subjects and animals 1 -9 . Plant sterols and stanols are not water soluble and possess low solubility in fats. It is believed that solubility characteristics affect the bioavailability and cholesterol-lowering efficacy of sterols and stanols. Thus, a large body of research has been conducted attempting to modify the structure of plant sterols and stanols, and the esterification to fatty acids 10,11 or ascorbic acid has been extensively studied in the past years 12 -14 . Accordingly, several different analogues of plant sterols and stanols are currently available as functional food ingredients or nutraceuticals.The interference with cholesterol incorporation into micelles has long been thought to be the possible mechanism by which plant sterols and stanols inhibit cholesterol absorption 15,16 . However, this mechanism cannot explain the observation that plasma cholesterol levels were significantly decreased in hamsters after plant sterols were injected intraperitoneally 17 . Recent advances in molecular research have indicated that the sterol transporter-mediated cholesterol efflux in the enterocytes and cholesterol secretion in the liver may play important roles in cholesterol absorption and metabolism 18...

Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters

“…While the higher hepatic triglycerides levels may contribute to higher VLDL-triglycerides secretion, higher hepatic total cholesterol levels may affect the expression of genes involved in cholesterol metabolism. Indeed, the 0AE3% cholesterol diet increased the expression of both hepatic ABCA1 and ABCG5, an effect already described in other studies involving hamsters under cholesterol-enriched diet [19,20]. Interestingly, hepatic expression of LDL-receptor and SR-BI was significantly reduced in dyslipidemic hamsters, which may be related to the higher hepatic total cholesterol content.…”

Use of hamster as a model to study diet-induced atherosclerosis

“…Hamsters fed a non-purified diet supplemented with 1% (w/w) cholesterol resulted in higher nHDL-C concentrations [117] compared to hamsters fed similar diets containing less cholesterol [0.1-0.2% (w/w)] [53,73,87,118]. Cholesterol added to semi-purified diets ranging from 0.1-0.3% (w/w) without supplemental fat resulted in similar nHDL-C concentrations [79,82,91,119,120]. There were no studies in hamsters fed semi-purified diets with greater than 0.3% (w/w) cholesterol in the absence of supplemental fat.…”

“…Compared to cholesterol-supplemented semi-purified diets [79,82,91,119], supplementing non-purified diets [53,87,117,118] with cholesterol, in the absence of supplemental fat, was reported to result in similar nHDL-C concentrations (Additional file 1 Figure S1B ). Noteworthy, cholesterol-supplemented semi-purified diets [79,82,91,119] without supplemental fat consistently resulted in higher HDL-C concentrations compared to non-purified diets [53,87,117,118] (Additional file 1 Figure S1A ).…”

Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the Golden Syrian hamster

“…This standard curve was used to calculate the relative levels of mRNA for the gene of interest and the reference/housekeeping gene (cyclophilin). Primers for ABCG1 and ABCA2 were previously described (45), as were primers for ABCG8 (46). Remaining primer sequences were 5′-ACTTTGGGCCTTTCTTTCGATGG-3′ (forward) and 5′-ATCTCTTTGTTCAGTGGAGGCCCA-3′ (reverse) for NPC1, 5′-TGAACCGCTTCTGGGATTACCT-3′ (forward) and 5′-AGTGCCGTCAGTTCTTGTGTGACT-3′ (reverse) for apoE, and 5′-TGGTTTCCAATAGGAGCAGGAGCA-3′ (forward) and 5′-TAAAGGACAGCGCCAAGACAGTGA-3′ (reverse) for NPC1L1.…”